(IAEA, 1986) (Fenech, 2005). If moderate deﬁciency in justone micronutrient can cause signiﬁcant DNA damage it isreasonable to be concerned about the possibility of additiveor synergistic eﬀects of multiple moderate deﬁciencies ongenome stability. Clearly there is a need to start exploringthe genotoxic eﬀects of multiple micronutrient deﬁciencies,as well as excesses, which are prevalent in human popula-tions. This aspect is analogous to genetic studies thatexplore, for example, the combined eﬀects of polymor-phisms in DNA repair genes on DNA damage.
4. Results from a recent epidemiological study suggest thatat least nine micronutrients aﬀect genome stability inhumans in vivo
We recently reported the results of an epidemiologicalstudy on 190 healthy individuals (mean age 47.8 years,46% males) designed to determine the association betweendietary intake, measured using a food frequency question-naire and genome damage in lymphocytes (Fenech et al.,2005a) measured using the CBMN assay (Fig. 1). Multivar-
iate analysis of base-line data showed that (a) highest tertileof intake of vitamin E, retinol, folic acid, nicotinic acid(preformed) and calcium is associated with signiﬁcantreductions in MN frequency, i.e.
49%, respectively, (all
< 0.005) relative tolowest tertile of intake and (b) highest tertile of intake of riboﬂavin, pantothenic acid and biotin was associatedwith signiﬁcant increases in MN frequency, i.e. +36%(
= 0.054), +51% (
= 0.021), and +65% (
= 0.001),respectively, relative to lowest tertile of intake (Fig. 2).Mid-tertile
-carotene intake was associated with an 18%reduction in MN frequency (
= 0.038), however, the high-est tertile of intake (>6400
46%) and theexacerbating eﬀect of riboﬂavin (+42%) on increased gen-ome damage caused by low folate intake. The results fromthis study illustrate the strong impact of a wide variety of micronutrients and their interactions on genome healthdepending on level of intake.As shown inFig. 3, the amount of micronutrients thatappear to be protective against genome damage varygreatly between foods and careful choice is needed todesign dietary patterns optimised for genome health main-tenance. Because dietary choices vary between individuals,due to taste preferences which may be genetically deter-mined or cultural or religious constraints, several options
V i t a m i n E C a l c i u m F o l a t e R e t i n o l N i c o t i n i c a c i d - C a r o t e n e R i b o f l a v i n P a n t o t h e n i c a c i d B i o t i n
P < 0.006
% v a r i a t i o n i n g e n o m e d a m a g e
Fig. 2. Percentage variation in genome damage rate for mid- and highesttertile of intake of vitamin E, calcium, folate, retinol, nicotinic acid, beta-carotene, riboﬂavin, pantothenic acid and biotin relative to the lowesttertile of intake. Genome damage rate was measured in peripheral bloodlymphocytes using the cytokinesis-block micronucleus assay. For moreinformation refer toFenech et al. (2005a).
A L M O N D S W H E A T B R A N C H E D D A R C H E E S E B R O C C O L I ( B O I L E D ) T U N A ( C A N N E D ) B E E F ( C O O K E D ) B A N A N A
AMOUNTS IN 100g EXPRESSED AS % OF MINIMUMREQUIREMENT FOR OPTIMUM GENOME HEALTH
Fig. 3. Content of micronutrients associated with reduced DNA damagein selected common foods. The height of each bar for each micronutrientwithin the separate foods corresponds to the amount of the micronutrientexpressed as the percentage of the minimum daily intake associated with areduced micronucleus frequency index in lymphocytes as determined inthe study of Fenech et al. (2005a). The relative contribution of each of themicronutrients (if present) is indicated by the height of each speciﬁcallycoloured bar. The nutrient content of the foods was determined usingpublished food content tables (Paul and Southgate, 1978).