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The following 29 studies show the possibility that PCBs increase kidney and urothelial cancer risks. This may not be a complete list of all kidney cancer research related to PCBs. For more, visit the TOXNET database operated by the National Library of Medicine (the source of these abstracts). Keep in mind that these kidney cancer studies are not all equal in size or quality. Some were published in peer-reviewed journals, while others were simply presented at conferences. A few are duplicates by the same author (one conference-based, another published) but we presented both because the descriptions were slightly different.
PCB exposure produced a consistent increase in kidney cancer
A review by researchers from the National Institute for Environmental Health Sciences used an analysis of combined occupational studies, and concluded that PCB exposure produced a “consistent increase in kidney cancer,” although the actual number of cases was small. (Longnecker et al, 1997) Study #2
higher numbers of kidney cancer for men followed PCB exposure
In January 1985, following a period of high electricity demand, an electric transformer located in a residential building basement and containing PCBs exploded in Reims. This led to the dispersion into the building of polychlorobiphenyls (PCBs) and trichlorobenzene from the inside of the transformer and the dispersion of PCB thermic breakdown products, especially furans (PCDFs) and dioxins (PCDDs). 343 people were exposed : firemen, EDF (French government-owned power company) workers, residents of the building and visitors. A medical follow-up was organised until 1990 when it was suspended due to a poor participation. However, it had to resume in 1994, due to health problems observed in personnel who had intervened during the accident. The RNSP (Public Health National Network) was commissioned by the Ministry of Health to make an epidemiological survey. Among the most
063 person years of employment. and the only notable finding was an association between machining fluids and kidney cancer. PCBs were classified as noxious substances. asbestos (1332214). machining fluids. A modification of the induction latency analysis method was used. fatigue. the 96/99/CE European Directive relating to PCBs and PCTs disposal has only been made French law in January 2001. Regressions with multiple exposures were also computed. and only after France has been rebukby the European Commission for not respecting deadlines set for the inventory phase for contaminated equipment and failing to present a disposal scheme. 1985: Total ban on further installation and use of equipment containing PCBs. 1987: Mandatory disposal of all equipment containing more than 100ppm. The study of cancer incidence revealed higher numbers of breast cancer for women. benzene (71432). The chemicals were pyranol (1336363). (Cordier et al. Despite this. Results showed that 28 exposure/cancer associations could be identified as important in the binary exposure regressions or in the contingency table screening. Site specific cancer deaths were regarded as cases. kidney cancer for men. machining fluids with kidney cancer. mixed solvents. itches and skin allergies have been noted. whereas a consistent positive association was evident between benzene and brain tumors. other solvents and lymphomas. Associations of resins with rectal and lung cancer. and resins with lung cancer. and TCE with leukemias seemed to be . important losses of memories.821 white male subjects with 51. and comparisons were selected from deaths considered unassociated with any of the exposures. and synthetic resins. The cohort consisted of 1. trichloroethylene (79016) (TCE). This accident led the French government to strengthen the existing legislation on PCBs: 1975: An order on behalf of the Public Health Code restricted the use of PCBs and rendered their disposal mandatory after use. 1983: An order on behalf of the Labour Code relating to labelling and packaging for hazardous substances was issued. Seven types of exposure with mutagenic or carcinogenic potential were rated together with the operations in which they were used. Pyranol lymphomas and solvent oral/laryngeal/pharyngeal cancers showed a greatly reduced association. Odds ratios (ORs) were calculated. 1996) Study #3 • machining fluids [including PCB-containing pyranol] were associated with kidney cancer A case/control study was carried out of cancer associated mortality at a transformer assembly factory in Massachusetts.frequently reported symptoms within the highly exposed group of people (75 people).
Traces of herbicides and pesticides and their products. Work history records were used to form the study cohort of 770 employees of Dow Chemical Company in Michigan. with 8 years work history as a painter in a transformer repair shop. (Shalat et al.5 total deaths and 52. although they had histories of occupational exposures to organic solvents. with a 14 year history of exposure to PCB oil as a linesman. The first was 34 years old with a 5 year history of extensive unprotected PCB contact as a painter in a transformer repair shop. While 242. The authors conclude that the link between machining fluids and kidney cancer is new. and that this as well as a possible association between lung cancer and resin systems deserve further investigation. The second case reported a chloracne like rash. and recommend an epidemiological investigation of renal adenocarcinoma in this industry.certain PCBs are dioxin-like] The cancer risks associated with pentachlorophenol (87865) (PCP) exposure were examined. and the third was 56 years old. Cross tabulation showed a similar association between level 2 solvents and reticulosarcoma. 1994) Study #4 • kidney cancer was reported in three utility workers exposed to PCBs Primary unifocal renal adenocarcinoma was reported in three caucasian male utility workers exposed to polychlorinated-biphenyls (PCBs). (Greenland et al. herbicides. solid cell sheets with mostly clear cytoplasm and a prominent vascular component (second case). The authors conclude that electrical utility workers are exposed to a variety of chemical and physical agents. The second was 43 years old. Pathological examination of the tumors showed solid cell sheets with eosinophilic cytoplasm and some cuboidal cells (first case). A modified life table approach allowed for the estimation of expected deaths and the calculation of standardized mortality ratios (SMRs). but no PCBs. 1989) Study #5 • deaths caused by kidney cancer increased significantly with increasing exposure to pentachlorophenol [contaminated with dioxin --. and clear cells in sheets as well as tubular and alveolar structures. electromagnetic fields and PCBs.6 deaths caused by malignant neoplasm were expected. were found in sera of the first two cases. observed deaths totaled 229 and . Industrial hygiene and process data were used to evaluate PCP exposure. None of the cases reported any personal risk factors.largely or entirely concentrated to post 1950 exposures. accompanied by a moderately dense inflammatory infiltrate (third case).
7.3.8) and renal pelvic cancer (RR 2. as well as in the groups exposed to 2.905. with an SMR of 357.8-tetrachlorodibenzo-p-dioxin (1746016) and other benzodioxins. a significant number of deaths was observed in the low exposure group. was used on census data to identify chemicals carcinogenic to the lower urinary tract. respectively. Other substances demonstrating increased risk of urothelial cancers were . and all accidents increased significantly with increasing exposure. or job/exposure matrix. the observation period was from 1961 to 1979. Exposure to some lubricating oils and fluids caused slight increase in the RR. cirrhosis of the liver. (Ramlow. dependent upon the source of combustion gases. Those in the remaining occupational groups were assigned to the unexposed group. Exposure to polycyclic aromatic hydrocarbons caused increases in the RR. and phenol (108952) judged as low to moderate in predictive value was found to increase the risk of bladder cancer (relative risk (RR) 1. Cases of urothelial cancer were identified through the Swedish Cancer Registry. However.660 employed males aged 20 to 64 years as of 1960. A significant excess of deaths caused by gastric or duodenal ulcer was observed. Fifty chemical compounds were chosen on the basis of prior identification as definite or probable urinary tract carcinogens.6). A total of 556. Analysis was restricted to the 1.429 were assigned to the exposed group. Although the excess in lymphopoietic cancer deaths was not significant. but may have been associated with some factor other than PCP exposure. and the positive predictive values for each link were characterized. Chemical process workers with exposures to unspecified aromatic amines were showed to be at increased risk of bladder cancer. Workers may have incurred an increased risk of death due to some specific causes. Exposure to creosote (8001589). gastric and duodenal ulcer. a trend toward higher risk with higher PCP exposure was evident. The exposed group was chosen from occupations in which at least 10 percent of persons in the job category had estimated exposures during the census year of at least 1 hour per week to any of the selected compounds. The authors conclude that this study does not support the possibility that PCP exposure increases the risk of liver and adrenal gland cancers.50. Links between exposures and work tasks were constructed. chlorinated phenols. The prevalences of death caused by kidney cancer. 1996) Study #6 • PCBs demonstrate increased risk of urothelial cancers [ includes kidney cancers] Classification of workers' exposure status by combinations of occupational title and industrial category.
The binding in liver microsomes is markedly increased by phenobarbital pretreatment. Rats were divided into 11 groups.3-Dibromopropanol (2. et al. Group 1 was given a DMN containing diet for 2 weeks.3-dibromopropyl)phosphate (Tris-BP) is activated to products which bind covalently to microsomal protein by a cytochrome P-450 dependent oxidation reaction. or 500 ppm PB. a hydrolysis product of Tris-BP. 1981) Study #8 • • PCBs promoted the production of nodules adenocarcinomas of kidney were composed of clear cells arranged in solid. The binding levels were 4 times higher to kidney DNA than to liver DNA. 1989) Study #7 • PCB pretreatment increased the protein binding of another kidney toxicant and carcinogen (Tris-BP) The nephrotoxicant and nephrocarcinogen tris(2. correlating with its relative organotoxic potential in single dose experiments. (Steineck et al. 2. A covalent interaction of Tris-BP with DNA could be demonstrated when DNA was added to liver microsomal incubations in vitro and to DNA extracted from liver and kidney after administration of Tris-BP in vivo.3-DBP). each group containing 20 animals. is also activated to covalently protein-bound products.chlorinated aliphatic hydrocarbons and polychlorinated biphenyls. Binding to proteins in the kidney was increased by pretreatment of animals with polychlorinated biphenyls. Administration of Tris-BP to rats leads to its covalent binding to proteins in liver and kidney.04 percent DMN. Binding to rat liver microsomes proceeds 15 times faster than with kidney microsomes. 500 parts per million (ppm) PCB. At week 5. (Soderlund. alveolar patterns The effects of polychlorinated biphenyls (PCBs) and phenobarbital (50066) (PB) on the induction of liver and kidney tumors by dimethylnitrosamine (62759) (DMN) were investigated in rats. animals underwent . the apparent Vmax of the reaction is 175 pmol/mg microsomal protein/min with control microsomes and 1053 pmol/mg protein/min with induced microsomes. with 5 times higher binding levels in kidney than in liver. but at a much slower rate than Tris-BP. a basal diet for 2 weeks and a PCB diet for 28 weeks. Male Fischer-344-rats were maintained on a diet containing 0. Binding with kidney microsomes is doubled after pretreatment with polychlorinated biphenyls.
The subjects were interviewed by questionnaire to obtain information on exposures.9. respectively. the group given DMN plus PB lost weight during the treatment. Two cases reported significant exposure to aromatic amines.9 and 2. and group 11 was given the basal diet. The authors conclude that PCBs and PB promote the production of nodules and hepatocellular carcinomas in rats pretreated with DMN. and other chlorinated organic compounds. aromatic amines. they were omitted from further analysis. group 6 was given DMN and PB. group 4 was given PCB alone.0 and 188.8.131.52. the liver was modular with tan nodules. respectively. Detailed information was sought on exposure to benzene. the RRs for benzene and PCB exposures were 2.5 and 2. alveolar patterns.unilateral nephrectomy (UN). Group 2 was given DMN and PCB diets without UN. asbestos (1332214). polychlorinated biphenyls (PCBs). Adenocarcinomas of kidney were composed of clear cells arranged in solid. and other industry related chemicals and the risk of urothelial cancer was conducted. with or without UN. Rats fed DMN and PCB showed decreased weight gain. group 8 was given PB alone. Sweden between 15 September 1985 and 30 November 1987 who were born between 1911 and 1945. The cohort consisted of 320 cases of urothelial cancer occurring in males living in Stockholm. In the kidneys of rats fed DMN alone. gasoline. Histopathological findings included rounded hyperplastic nodules with compression of normal liver tissue and constituent hepatocytes were larger than normal. and other products. Cholangiofibrosis demonstrated severe bile duct proliferation with prominent fibrosis. After adjusting for year of birth and smoking. group 7 was given PB plus UN. . combustion gases from coal. group 10 was given DMN alone. All animals were sacrificed at week 32 and complete autopsy was performed. group 3 was given PCB plus UN. grey nodules were also observed. and smoking and dietary habits. after adjusting for year of birth and smoking A case control study of the association between exposure to benzene (71432). In the rats fed DMN and PCB. occupational history. Hepatocellular carcinoma demonstrated irregular trabecular arrangement of hepatocytes and was indicated by nuclear hyperchromatin and increased mitotic index. group 5 was given DMN and PB with UN. Crude RRs for exposure to benzene and PCBs were 1. (Arai et al. The referents consisted of 363 randomly selected residents of Stockholm. group 9 was given DMN plus UN. exhausts. The urothelial cancer relative risk (RR) for current and former smokers was 3. cutting fluids. 1983) Study #9 • urothelial cancer [including kidney cancer] relative risks for PCB exposures were 3.
certain industry-related chemicals were judged as warranting further attention as possible urothelial carcinogens.5. The risk depends on mean annual dose and exposure has to start at least two decades before the observation period. such as nitroarenes or polycyclic aromatic hydrocarbons. Two cohorts were followed up and a case-referent study was made in the county of Stockholm in 1985-87. we find some support for the hypothesis that exposure to chlorinated aliphatic hydrocarbons increases the risk of urothelial cancer. For creosote. and polychlorinated biphenyls. When categorized by occupation and industry. respectively. Subjects exposed to benzene who also had high dietary intakes of fried foods and fat had RRs of 9. (Steineck et al. 1990b) Study #11 • one cohort study gave some support for PCBs being associated with urothelial cancer The purpose of this thesis was to identify the risk factors for urothelial cancer.8 compared to those taking vitamin-A. The risk due to benzene exposure increased with increasing estimated dose for subjects who had been exposed for at least 20 years before the study. the epidemiologic literature of cancer of the lower urinary tract is evaluated for these substances. data are scarce (prior to 1990) In a previous cohort study by our group. hair dyes. Current smokers exposed to benzene had an RR of 7. The authors conclude that exposure to benzene is associated with an increased risk of urothelial cancer. In this paper. cutting fluids and cutting oils.7. Furthermore. 1990a) Study #10 • for PCBs and urothelial cancers. After controlling for any annual exposure to benzene the RR was reduced to 5.1. however. the highest risk was associated with employment in the rubber industry. It is. data are scarce. Pipe smoking increased and intake of supplements (mainly containing vitamin A) decreased the risks. Available data do not support the hypothesis that asbestos is associated with urothelial cancer.1.3 and 10. uncertain whether this risk is due to contaminants of aromatic amines in tar volatiles or whether it depends on other agents.respectively. Subjects exposed to benzene who were not taking vitamin-A supplements had an RR of 5. "Publication bias" such that only limited (Steineck et al. Cases who had moderate or high annual exposures to gasoline and diesel exhausts had an RR of 7. The hypothesis . We would like to add combustion gas/soot from coal to the substances considered as increasing the risk urothelial cancer.
not a biological phenomenon. possibly compromising the positive predictive value. polychlorinated biphenyls (PCBs) and creosote as increasing the risk of urothelial cancer. The reverse is true for confounding factors. creosote and polychlorinated biphenyls being associated with urothelial cancer. benzene was identified as a possible risk factor. among industry-related chemicals. we expand on some theoretical issues.g. One should not confuse different levels of the positive predictive value with exposure dose. Confounding from industry-related agents arises due to a true mixed exposure in certain work tasks. Studies with exposure information from a job-exposure matrix applied to registers with scant information on occupation and industry may be warranted for exposures and diseases for which previous studies with a detailed documentation of exposure have low precision. and present detailed accounts of constructed linkages for PCBs. 1993) Study #13 • • PCBs altered kidneys’ histopathology PCB congener 118 accumulated in kidneys . creosote. to avoid residual confounding after restriction to subjects unexposed for the confounding factors. (Steineck. In this article. have convincingly been linked to urothelial cancer. For agents of interest. one should emphasize sensitivity. In the epidemiological literature. and phenols. A dose-response relationship was also seen with an increasing average daily intake of fat. This discrepancy between agents of interest and confounding factors may limit the application of a general matrix for studying several different diseases. e. One cohort study gave some support for combustion gases from coal. identifying. A "dose-response" with different levels of positive predictive value reflects an accuracy of the matrix. but also due to a gross classification of occupations in the census. one should emphasize the positive predictive value rather than the sensitivity in the construction of the matrix. if sensitivity rather than positive predictive value is emphasized for an agent.that intake of browned material formed during cooking is an important risk factor was supported in a case-referent study. The construction of the matrix is much harder. (Plato et al. 1990c) Study #12 • PCBs increased risk of urothelial cancer We have previously reported a study in which a job-exposure matrix was applied to census data. In the case-referent study.. only certain combustion gases from coal. besides aromatic amines.
kidneys.000ppb PCB-77 were noted. measurable PCB-77 levels were detected only in the fat and liver of the highest dose animals. Increases in the absolute and relative spleen weights of male rats treated with 1. spleens.000 parts per billion (ppb) PCB-77 or PCB-118 for 13 weeks. A dose dependent accumulation of PCB-118 was noted in the fat and liver of treated animals with lower levels identified in the kidneys.7 micrograms/kilogram body weight per day while that for PCB-118 was 200ppb in the diet or 17 micrograms/kilogram body weight per day. No clinical evidence of toxicity was observed. An increase in the concentration of 3.000ppb PCB-118 exhibited significant decreases in levels of dopamine and homovanillic-acid in selected areas of the brain. Workers in the high and low serum PCB groups from that study were invited to participate. and hearts.4-dihydroxyphenylacetic-acid was seen in the brains of males exposed to the highest dose of PCB-77 while females treated with 2. Use of PCBs was discontinued in 1977. The effects of PCB-77 and PCB-118 on various biological parameters were assessed following treatment of SpragueDawley-rats with up to 10.3'.3'.4'. Those in the high level group were on the average 5. In contrast. Bloomington.4. a follow up study was conducted of workers occupationally exposed to polychlorinatedbiphenyls (1336363) (PCBs) at the Westinghouse Electric Corporation's Transmission and Distribution Components Division (SIC-3629). Histopathologic treatment related alterations were identified in the livers. By 1985 the levels of serum PCB concentrations in the low group had decreased by an average of 85% of the . 60 of 66 workers originally studied participated in this study. Treatment related biochemical changes included increases in the activity of hepatic microsomal ethoxyresorufin-Odeethylase in animals treated with the highest doses of PCB-77 or PCB-118.000 or 10. Indiana. and bone marrow of both PCB-77 and PCB-118 treated animals.6 years older than the low PCB group. thyroid glands.A study was conducted on the toxic effects of 3.4.5-pentachlorobiphenyl (32598144) (PCB118) following dietary exposure.4'-tetrachlorobiphenyl (32598133) (PCB-77) and 2. brains. 1995) Study #14 • • PCBs had physiological effects on kidney function long-term cancer risks (beyond 8 years) were not followed In response to a request from the Indiana State Board of Health. A cross sectional study had been conducted in 1977. Based on these data the no observed adverse effect level for PCB-77 was calculated to be 100ppb in the diet or 8. A significant decrease in the liver vitamin-A content was seen as well in animals treated with the highest dose of PCB-77. (Chu et al.
small intestine. Cytochrome P4501A1 immunoreactivity was measured as a marker of Aryl hydrocarbon Receptor pathway activation in liver. juvenile flatfish in shallow coastal bays. In summer flounder. (Steele et al. stomach. and grown out for 3 weeks to assess mortality. CYP1A1 induction was highest in the kidney and liver. In the younger group we . total bilirubin. Larvae were exposed to radiolabeled CB 126 through the water. is a commercially important species of flatfish found on the East Coast of the United States. this pattern was in accord with observations in other species. According to the authors. The clinical significance of these findings 8 years after occupational exposures had ceased is unknown. respectively). Levels in the high PCB group had decreased by an average of 90%. PCBs are among the major pollutants found in industrially impacted coastal ecosystems. metamorphosis is regulated by thyroid hormones (TH).9 pg/mg and 170 pg/mg. The younger group appeared more sensitive than the older (LD 20 = 20. the biochemical findings are indicative of the physiological effects of PCBs on lipid metabolism. serum apolipoprotein-B. and urinary alanine-aminopeptidase. Paralichthys dentatus. urinary creatinine. Pelagic. stomachless larvae metamorphose into the benthic. and chemically induced hypothyroidism inhibits metamorphosis past the very early stages. gastric. beta-glucuronidase. and was maximal near the LD 20 in all tissues. lagoons and estuaries during the spring. Fundulus heteroclitus). Mean metamorphic stage was calculated at the end of growout to determine if sublethal doses had an effect on metamorphosis. Serum PCB levels were positively and significantly correlated with triglycerides. Here we present results of the first experiments carried out 30-day-old (premetamorphic) and 39-dayold.1977 value. serum apolipoprotein-Al. (early metamorphosing) larvae to establish their sensitivity to CB 126. and kidney. conjugated bilirubin. from Cape Hatteras to Maine. This project is concerned with determining the developmental effects of the dioxin-like CB 126 on metamorphosing larvae.g. liver function and kidney function. lowest in anterior intestine. No clinical abnormalities attributable to PCB exposure were noted. and are known to act as endocrine disrupters by lowering blood TH levels in mammals and some fish. Sensitivity to CB 126 was similar to that observed in embryos of other marine fish (e. cholesterol. 5'nucleotidase. 1990) Study #15 • • PCB-induced enzymes were highest in the kidney and liver this pattern was in accord with observations in other species The summer flounder. and ultimately to understand if any of the effects are mediated by thyroidal disruption.
2002) Study #16 • • PCB mixture Aroclor 1248 caused loss of kidney cell viability and cell death in a concentration.2'. . Cellular alterations in liver. and intestine were all linked to seasonal changes. The two PCB congeners assessed can also induce apoptosis. Histopathological study of bream (Abramis brama) and asp (Aspius aspius) living in a PCB-polluted freshwater lake revealed abnormal cellular changes in the renal corpuscle of both species. The results suggest a different molecular mechanism in the induction of apoptosis by planar or nonplanar PCB congeners. 2001) Study #17 • PCBs were associated with abnormal cellular changes in the renal corpuscle (kidneys) The purpose of this study was to evaluate the potential toxic effects of chronic sublethal polychlorinated biphenyl (PCB) exposure on feral fish. gill. The results suggest that some of the observed histopathological changes in renal glomeruli.and time-dependent manner individual PCB congeners produced kidney cell death by different mechanisms The effects of a commercial polychlorinated biphenyl (PCB) mixture (Aroclor 1248) and two individual PCB congeners were evaluated on rat renal proximal tubule culture cell viability and internucleosomal DNA fragmentation (DNA ladder) characteristic of apoptosis.observed a dose-dependent trend toward more advanced metamorphic stage.4'. However.4-tetrachlorobiphenyl) than for the di-orthosubstituted nonplanar congener (2. (Soffientino et al.4. (Perez-Reyes. or totally absent in fish caught from reference locations. the extent of apoptosis generated was greater for the non-orthosubstituted planar congener (3. suggestive of an effect of CB 126 on developmental rate. gonads.3'. and filling of Bowman's space (FBS). an adhesion between visceral and parietal layers of Bowman's capsule (ABC).5. using histopathology as an endpoint. et al.4. Dilation of glomerular capillaries (DGC). The prevalence of each of these lesions was significantly lower. were highly prevalent features in lake fish.and timedependent manner. mesangial edema (ME). spleen. Treatment with Aroclor 1248 caused the loss of cell viability and promoted apoptosis in a concentration.5'-hexachlorobiphenyl). This correlated with the loss of cell viability since the planar compound is much more cytotoxic.
3'. TRI-induced renal dysfunction was potentiated by dietary PBB and dietary PCB.1. could possibly indicate a prolonged chemical stress caused by PCBs and related compounds. 20 or 100 ppm PBB for 20 days were subsequently injected with various doses of CCl4 and 96 h LD50 values were determined. injections of various quantities of trichloroethylene (TRI). and greater in PBB-treated than in PCBtreated mice. 2001) Study #18 • PCBs increased the kidney dysfunctions caused by trichloroethylene exposure Several polyhalogenated biphenyls are known to be ubiquitous environmental contaminants. PBB appeared to be more potent in this respect. 1979) Study #19 • low amounts of PCBs were enough to modify kidney cell membrane fluidity The influence of different polychlorinated biphenyls (PCBs) upon dynamic properties of membranes from rat renal tubular cell cultures has been investigated.4'- .particularly DGC and ME. It is also possible that chronic PCB exposure may have suppressed and weakened the immuno systems of exposed fish making them more vulnerable to secondary parasitic infections. Functional damage to the liver (elevated serum glutamic oxaloacetic transaminase activity) was not produced by acute administration of TRI. 1. CCl4-induced liver damage was greater in PCB-treated mice than in controls. Functional renal damage (elevated blood urea nitrogen concentration. Male ICR mice were fed a control diet or the same diet supplemented with 100 ppm polybrominated biphenyl (PBB) or 200 ppm polychlorinated biphenyl (PCB) for 28 days before single i.4. tetrachloroethylene (TET). TET or TCE.2trichloroethane (TCE). The LD50 CCl4 was lower in mice treated with 20 ppm PBB than in control mice and lower in mice treated with 100 ppm PBB than in those treated with 20 ppm PBB. (Kluwe et al. and two pure PCB congeners: 3. Studies have been realized with Aroclor 1248 (a commercial PCB mixture with 48% chlorine by weight). Both TCE-induced and CCl4induced renal dysfunction were potentiated by dietary PBB but not by PCB. or carbon tetrachloride (CCl4). decreased organic anion transport capacity) was produced by acute administration of all solvents except TET.p. Mice fed a diet containing 0. The ratio of liver weight to body weight was increased by dietary PBB and dietary PCB. (Koponen et al.
5'hexachlorobiphenyl (an ortho-substituted nonplanar congener). Canada.4'. (1968 and 1970) show that twice as much PCB as DDT has been found in the tissues of some seabirds in San Francisco Bay. renal damage and reduction in size and/or atrophy of the spleen. et al. The changes include moderate atrophy. rats and rabbits. . The main effect of PCBs in birds are increased fluid in the pericardial sac. No definite work has been done to establish LD50 values for the various formulations of PCBs.2'. Even though rat renal tubular cell cultures accumulated only a low amount of PCBs when cells were incubated in presence of the toxicant. The DDE rate is lowest near industrial areas.4'.5. The most important effects of the PCBs are their longrange sublethal effects. the Netherlands and from the United States. necrosis and weight increase.5. guinea pig and rabbit as well as in the chicken and Bengalese finch are summarized.4. Changes in the membrane fluidity were measured by the fluorescence polarization technique using the probe diphenylhexatriene. 1997) Study #20 • kidney damage is one of the main PCB effects in birds The current knowledge about polychlorinated biphenyls (PCBs) including the toxicology of these compounds as well as the levels of PCBs found in nature is summarized and evaluated. at least in industrial areas. The treatment of cells with Aroclor 1248 increased membrane fluidity in a dose-dependent manner. Sweden. Germany. PCB residues have been found in wild life from Great Britain. A fair amount of information has been collected about PCBs but the toxicology of these compounds is poorly known in comparison to that of chlorinated pesticides. Recent studies by Risebrough et al. More research is needed to ascertain the presence of PCBs in higher forms of life and the effects of this presence. Evaluation of the available data on PCBs in tissues tends to parallel that of DDE. strong legislative control should be enacted to stop it. a significant increase of membrane fluidity was found in presence of 2. Finding the major source(s) of PCBs entering the environment is the most critical area for research. The most common ones in the rat. PCBs mainly cause pathological changes in the liver of guinea pigs. A number of studies including acute single dose. acute feeding and sublethal dose experiments are cited. but no significant dif [incomplete abstract] (Lopez-Aparicio.4.2'. Like DDT. Once the leak is found. indicating that PCBs are not carried quite as readily to remote areas.tetrachlorobyphenyl (a coplanar compound) and 2.5'-hexachlorobiphenyl. PCBs are capable of accumulating as they advance up the food chain. that small quantity was enough to modify the membrane fluidity. Interestingly.
in the kidney.3'.4. Renal toxicity of chloroform was reduced by TCDD or PCB pretreatment. microsomal enzyme activities were increased by PB. The induction of various drug metabolizing enzymes or retinyl-palmitate-hydrolase activity.4. The polychlorinated biphenyls (PCBs) were given in doses of 300 micromoles/kilogram (micromol/kg).4'-tetrachlorobiphenyl (32598133). Pretreatment with TCDD. and DDT was a given at a dose of 150micromol/kg. but not the other PCBs.5.2'. primarily retinol.2'. TCDD and PCB. decreased total liver vitamin-A content within 7 days of administration. It is suggested that chemical or redox changes in the liver as a result of the toxicity of the xenobiotic may result in the nonenzymatic destruction of the liver vitamin-A stores. No effect of chloroform toxicity to the liver was noted by pretreatment with 3MC or PCB's.4'. a key enzyme in hepatic retinyl-palmitate hydrolysis. 3.Study #21 • • kidney enzyme activities were increased by PCBs kidney toxicity of chloroform was reduced by PCBs ICR mice were treated with phenobarbital (PB).5'hexachlorobiphenyl (35065271) to male Sprague-Dawley rats. Even so. however. the rise in kidney vitamin-A was minimal compared to its loss from the liver. but no effect by PB was noted on kidney damage caused by chloroform. These results suggest that the chloroform metabolites ultimately responsible for renal and liver damage are not generated at a common site. . decreased hepatotoxicity of chloroform. or 2. Study #22 • certain PCBs decreased liver Vitamin-A content 60% within 7 days. Toxicity of chloroform to the liver was increased by PB pretretment.4'-tetrachlorobiphenyl. and increased kidney Vitamin-A levels 3-fold The kinetics of liver and kidney retinol and retinyl-palmitate levels were examined following single intraperitoneal injections of DDT (50293). Administration of 3. The metabolite probably responsible for liver damage is apparently generated in the liver.4.3'. Hepatic.5. 3-methylcholanthrene (3MC). was not implicated in the depletion of hepatic vitamin-A. but not renal. the one responsible for kidney damage. 2. Renal and hepatic microsomal enzyme activities were increased by 3MC. accompanied he decrease in liver vitamin-A.5'tetrachlorobiphenyl. This decrease left vitamin-A levels of 40 percent of control animals. TCDD or PCB. and similarly. A three fold rise in kidney vitamin-A.
Studies of the distribution of carbon-14 labeled PCBs in mice were discussed.5-PCB.4.5-PCB).5-PCB increased cytochrome-P-450 content and the activities of aminopyrine-Ndemethylase and aldrin-epoxidase in liver. A significant increase was noted in kidney retinol content.2-bis-(4chlorophenyl)ethane (50293) (DDT) and several prototypic polychlorinated biphenyls (PCBs).5.4. Dose and structure dependent accumulation and long term retention of the compounds in the tracheobronchial mucosa have been observed. Radiolabeling studies have .4.Study #23 • certain PCBs caused significant increases in kidney retinol (VitaminA) content Changes in vitamin-A parameters were compared with the kinetics of induction of various drug metabolizing enzyme activities using 1. Weanling male Sprague-Dawley-rats were given a single intraperitoneal injection of a synthetic PCB at 300 micromoles/kilogram (micromol/kg) or DDT at 150micromol/kg. DDT and 2. and uridine-diphosphateglucuronosyltransferase activity. No change was noted in any vitamin-A parameter in DDT or 2. No highly significant correlations were found among the vitamin-A levels and drug metabolizing enzyme activities in the liver. and 5 following treatment.4. PCBs used included 2.4.5-PCB exposed livers. 1987) Study #24 • sulfur-containing PCB metabolites accumulate in the kidney Studies of the tissue distribution of polychlorinated biphenyls (1336363) (PCBs) in laboratory animals were summarized.4-PCB altered serum retinol levels.4'. 5.3'.1-trichloro-2.2'.4'-tetrachlorobiphenyl (32598133) (3.5' positions.5'-tetrachlorobiphenyl (2. Only marginal changes in drug metabolizing enzyme activities were induced by 2. The greatest accumulation occurred in PCBs having chlorines in the 2. Twenty eight PCBs and six chlorinated compounds which are not PCBs were investigated.2'. with decreases on days 1. aryl-hydrocarbon-hydroxylase.4'. 3.4-PCB showed a significant decrease in whole liver vitamin-A content during the first week following treatment.5.4PCB was a potent inducer of cytochrome--P-450 dependent benzo(a)pyrenehydroxylase.4. or 7 days thereafter.5-PCB and 3.2'. or 2.4-PCB). 3.5'hexachlorobiphenyl (35065271) (2.5. Rats were sacrificed 1. (Azais et al. Most of the PCBs were present as 4-methylsulfonyl metabolites. Only rats treated with 3.5-PCB). Only 2.1. 3.4-PCB also decreased liver total vitamin-A content and levels of serum retinol and caused a significant increase in kidney retinol. 3. Treatment with 3.
and apparently depends on the nature of the substituent in the para position. and were separated into ribosomes and into the postmicrosomal supernatant fraction. The latter fraction from liver and kidney was used to prepare the pH 5 supernatant fraction. Accumulation of PCB metabolites in sites outside the lung and kidney were discussed. containing elongation factors 1 and 2 (EF 1 and EF 2) for protein biosynthesis. the ventral prostate and large intestinal epithelium of rats. we have investigated the effect of dietary exposure to Aroclor 1254 (1-100 ppm) given chronically or discontinuously over an 84-day time interval to the female F344 rat. 1987) Study #25 • PCBs increase the protein synthesizing activity of kidney pH 5 supernatant fractions Homogenates of liver and of kidney cortex were obtained from control rats and from rats treated with the polychlorinated biphenyls (PCBs) Aroclor 1254. Studies on the accumulation of MeSOPCBs in kidney proximal tubular cells in mice were discussed. and the cerebral gray matter of quail. This proteineSOPCB complex has been shown to be subsequently secreted into the airway lumen and spread over the entire surface lining. Tissue binding of sulfur containing PCBs which are not xenobiotics was considered. liver and adrenal cortex. Studies with dimethylsulphone (67710) and chlorinated benzenes in mice have shown that sulfur containing metabolites accumulate in the lung. kidney. These have shown that the extent of accumulation is different from that of the lung. (Cappon et al. These fractions were incubated with KCl-washed ribosomes obtained from control rat liver. The elongation factor 1-dependent binding of (14C)phenylalanyl-tRNA to ribosomes was also markedly increased both with the liver and the kidney preparations obtained from the rats that had received PCBs. Cytochrome P4501A was quantified in lung and kidney by measuring the dealkylation of ethoxyresorufin substrate and by . (Brandt et al. The incorporation of (14C)phenylalanyl-tRNA into peptide was increased with the liver and kidney preparations derived from the treated rats.indicated that the 4-methylsulfonyl PCB (MeSOPCB) metabolites are bound initially to a specific MeSOPCB binding protein in the Clara and goblet cells. MeSOPCBs have been found in the uterine and fetal soft tissues of mice. 1976) Study #26 • kidneys are more sensitive than lungs to PCB enzyme induction In this report.
although the persistence of the induction re [incomplete abstract) (Beebe. At 2 weeks three out of seven and at 6 weeks four out of seven lung I-spots were lowered by 51100% in the Aroclor 1254-treated rats. At both time points Aroclor 1254-treated rats had significantly lower body weights and higher liver weights while kidney and lung weights were unaffected. These data demonstrate the sensitivity of kidney to P4501A induction capacity as compared to lung. on I-compounds (tissue.and time-dependent increase in both extrahepatic organs. 2 weeks apart) into 3-month-old rats. In treated rats there was no decrease in kidney I-spots at 2 weeks. while kidney DNA showed a small decrease at 2 weeks. species and sex dependent DNA modifications that increase with age in untreated rodents) were studied by 32P-postlabeling in male Sprague-Dawley rat liver. Treatment resulted in significant reductions (ranging from 29 to 100%) of each of nine liver I-spots at 2 and 6 weeks.) injected (2 X 500 mg/kg. Since Aroclor 1254 has been reported to be a tumor promoter in liver and lung but not kidney. (Nath et al. kidney. The kidney appeared to be more responsive to induction than lung at all doses (maximum of 500-fold induction following 84 days exposure to 100 ppm). Aroclor 1254 was dissolved in corn oil and intraperitoneally (i. but not kidney cancers.Western immunoblotting. and lung DNA. The decline in 1A induction observed following discontinuous exposure was more prominent in the kidney than in the lung. Control rats were given corn oil. these results suggest a correlation between organ specific promotion of carcinogenesis by Aroclor 1254 and the reduction of DNA I-compounds. Thus the effects decreased in the order liver > lung > kidney. Groups of 3 animals were sacrificed at 2 and 6 weeks after the second injection of corn oil or Aroclor 1254. Aroclor 1254. in rats treated with nitrosamines .p. immunoblotting and Northern analysis of total RNA for the presence of 1A2 in the most highly induced kidneys. there was evidence by enzymatic activity. 1991) Study #28 • PCBs promoted liver cancers. 1995) Study #27 • PCB mixture Aroclor 1254 altered liver and lung tissue more than kidney tissue The effects of a tumor promoting polychlorinated biphenyl mixture. Thymidine incorporation into liver and lung DNA was significantly increased at both time points. P4501A displayed a dose. while the levels of only two out of ten kidney spots were reduced by 42-91% at 6 weeks. et al. Further.
(Hirose et al. HANOVER.The effects of phenobarbital (PB). respectively.05% PCB or 5% SS for 32 weeks. In two ongoing case-control studies on kidney cancer and. and on the criteria adopted to define relevant exposure. 1993) Upcoming Research SINCLAIR JA. These criteria are difficult to standardize and are rarely made explicit in published reports. The incidence of hepatocellular carcinoma was much higher in rats given PB or PCB than in controls given EHEN alone. The rats were given 0. One further questionnaire was used to collect details of task and environment for all the other activities. specifically addressing industrial activities where the knowledge of job title alone would have been insufficient for reliable exposure assessment. which makes it difficult to interpret inconsistencies among different studies. PB administration significantly decreased the average number of renal-cell tumors per unit area and SS reduced the numbers of early neoplastic nodules. 0. on the knowledge of the specific industrial process by the experts. intensity and frequency of exposure to 30 substances known [incomplete abstract] (Belletti et al.05% PB.1% EHEN in their drinking water for 2 weeks and then diet containing 0. These data are used to establish probability. Treatment with PCB had no effect on renal carcinogenesis. EFFECTS OF ARSENIC ON CYTOCHROME P450 Source: Crisp Data Base National Institutes of Health. polychlorinated biphenyl (PCB) and sodium saccharin (SS) on hepatic and renal carcinogenesis induced by N-ethyl-Nhydroxyethylnitrosamine (EHEN) were examined in male F344 rats. a detailed occupational history was obtained and supplemented by 19 additional questionnaires. These results indicate that chemicals may have either a promotive or inhibitory effect depending on the organ. In week 3.study may correlate PCBs and kidney cancer The validity of retrospective assessment of occupational exposure greatly depends on the amount of detail in the available information. Author Address: DARTMOUTH MEDICAL SCHOOL. NH 03755-3835 • • arsenic modulates the accumulation and elimination of PCBs arsenic is associated with kidney cancer . the right kidney was removed to promote renal neoplasia. malignant lymphomas. 1981) Study #29 • incomplete abstract --.
understanding their effects when present in combinations will be important for our overall evaluation of the health effects of these agents. and therefore these effects may contribute to arsenic. that have not previously been appreciated. The overall goal of this project is to determine the effects of arsenic (II I) and other selected metals on specific liver CYPs. and over 60% of these sites contain toxic metals. and kidney cancer. bladder. In particular. and the ability of arsenic to modulate accumulation and elimination of polychlorinated biphenyls and drugs.induced cancer and vascular disease and/or enhance the toxicity of other chemicals. which might occur in Superfund sites containing arsenic in combination with other metals and organic contaminants. lung. Our previous studies have demonstrated in hepatocytes in culture that low concentrations of arsenic significantly decrease induction of several major CYPs. We hypothesize that these effects occur mainly at the posttranscriptional level. Previous work in this and other laboratories has demonstrated that arsenic can have substantial effects on specific cytochrome P450s (CYPs) that are principally responsible for metabolism of drugs and other xenobiotics by the liver. We hypothesize that arsenic-induced alterations in CYP mediated xenobiotic metabolism may have a significant impact on the response of humans and other organisms to other toxic chemicals. High levels of arsenic in drinking water are associated with an increased risk of skin. the post-transcriptional mechanisms by which arsenite specifically decreases synthesis of rat CYPA23 and chick CYP2H1. These arsenic mediated decreases are not due to the induction of heme oxygenase. These studies may provide insight into effects of arsenic and other toxic metals. or oxidative damage as had been previously postulated. lung and other organs. depletion of heme. Our specific aims will be to: 1) determine in intact rodents the effects of acute and chronic exposure to arsenic (III) on induction of CYPs. . arsenic exposure decreases the induction of CYPs by chemicals that are subsequently metabolized by these CYPs. in cultured hepatocytes. in combination with exposures to other toxic agents.• • PCB accumulation may boost arsenic’s tendency to produce kidney cancer [Northeast Wisconsin has many areas of high arsenic levels in drinking water] Arsenic is found at high levels in almost half of all Superfund sites as well as many public and private water supplies in the northeastern and western regions of the United States. This is postulated to increase the bioaccumulation of other toxic chemicals. and 2) determine. Since most Superfund sites and other waste sites contain complex mixtures of toxins.
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