Helen Mendenhall and Miranda Laskey

The Genetic Effects of Nitrous Oxide Emissions

The Compound/Gene/Protein
Nitrous oxide (N​2​O) is a chemical compound that is prevalent in terms of pollution as
well as medicinal purposes. This greenhouse gas slowly depletes the ozone layer because it is
extremely potent, and it also absorbs radiation which contributes to climate change and global
warming in the atmosphere (Spiro, 2012). The main source of N​2​O emissions is from agriculture
(Spiro, 2012). Aside from its environmental impact, N​2​O is known as “laughing gas” because of
the euphoric effects one experiences from directly inhaling it. This gas can be used as an
anesthetic in high doses (Nagele, 2014). Being that N​2​O shows up in various aspects of life, the
effects that it could have on people have been researched extensively.
N​2​O has been shown to cause mutations to the ​methylenetetrahydrofolate reductase ​gene
(MTHFR). Studies have focused on how this compound reacts with/effects mechanisms within
the body when inhaled for anaesthetic purposes.The MTHFR gene serves as an instruction
manual for the creation of an enzyme called ​methylenetetrahydrofolate reductase which aids in
processing amino acids (Selzer, 2003). The protein that is made is called the MTHFR protein.
The MTHFR enzyme produces methylfolate in regards to the methylation. This helps the body
process folate, which is needed to make DNA and regulate proteins in general. Folate is
converted from the form​ 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate which is
the usable and active form of folate (Selzer, 2003). The proteins involved are referred to as folate
binding proteins. 5-methylenetetrahydrofolate is used to convert homocysteine to methionine
(both amino acids). The signaling cascade is outlined below. This methylation cycle is very
important for making DNA and overall body functioning (Selzer, 2003).

The Mutation
 Helen Mendenhall and Miranda Laskey

N​2​O has caused mutations to the MTHFR gene which alters the regular pathway and can
lead to several health issues. Mutation in this gene can lead to genetic complications and
disorders such as spina bifida, anencephaly,IBS, autism, fibromyalgia, etc (Coleman, 2019).
N2O can inhibit vitamin B12 through the oxidation of cobalamin, and subsequently inhibits
enzymes that affect methionine synthesis (Nagele, 2014). The pathway is impacted and changed
of the oxidation that N2O caused in cobalamin (vitamin B12) because it sets up for the
methylation with methylfolate to occur (Nagele, 2014). Methylfolate is what is produced by the
MTHFR enzyme. When the pathway is altered, a lack of vitamin B12 can impact development
by affecting the production of red blood cells which limits oxygen transport throughout the body
(Nagele, 2008). This mutation was not necessarily found to affect one gender more than another,
yet studies have shown that complications arising with the MTHFR gene mutation may cause
mortality in men more than women (Heijmans, 1999).

Treatment/Remediation
Since nitrous oxides have adverse effects on the environment and hold the ability to cause
mutations in genes, it is important to find a way to limit the amount of N​2​O emissions in the
atmosphere. In a study that examined the effects of nitrous oxide of Swedish midwives, proper
use of equipment can reduce exposure levels in delivery rooms and dental offices. It was also
found that exposure levels in Sweden were significantly lower than in the United States
(Axelsson 1996). As it’s seen globally, oftentimes one of the most important ways to combat
illness or destruction of health is through education. It’s crucial to set healthy guidelines on how
to safely use equipment and to recommend precautions when doing so. Setting proper guidelines
and training those using equipment used in the release of nitrous oxides on proper safety
precautions limits their risk of adverse effects. In turn, it also limits the adverse effects found in
 Helen Mendenhall and Miranda Laskey

patients exposed to the equipment as well. Since it was found that exposure to nitrous oxides in
patients with severe MTHFR gene mutations only increases symptoms, it is important to take
preventative measures in eliminating the accelerated symptoms. For example, since many dental
procedures require patients to undergo anesthesia it is recommended that patients are screened
before undergoing these procedures (Selzer, 2003). If health care workers are trained properly on
true consequences of continuous exposure to nitrous oxides when containing this mutation, this
will result in an increase in screening before procedures and a reduction in exposure.
Environmentally, in order to decrease the amount of nitrous oxide emissions in soils,
denitrification is found to be successful at reducing nitrous oxide to nitrogen (Smith, 1998).
Denitrification is the elimination of nitrogen in the form of atmospheric nitrogen (N​2​).
Converting nitrous oxide to atmospheric nitrogen is possible by the addition of nitrous oxide
reductase in soil. This strips the nitrous oxide of oxygen and is eliminated from the soil into the
air (Alvarez, 2013). It was also found that nitrous oxide levels increase with temperature. Nitrous
oxide emissions seemed to increase in April and June when compared to the rest of the year, but
the respiratory demand for atmospheric oxygen should be examined as a potential increase in
nitrous oxide emissions (Smith, 1998). Finding a way to keep crops at lower temperatures, or
away from plants that require high levels of atmospheric oxygen to successfully grow will allow
for a limited level of nitrous oxides found in the soil.

Graph

Figure 1.​ Human impact on nitrous oxide emissions (whatsyourimpact.org)

Partaking in preventative measures seems to be one of the biggest takeaways from these
studies. High and constant exposure to nitrous oxides in soil chemistry can increase risk of
MTHFR gene mutations that can lead to genetic complications and disorders. It’s important to
 Helen Mendenhall and Miranda Laskey

combat these potential life complications with preventative measures such as screening those
who are about to partake in dental procedures and can be exposed to nitrous oxides, and
educating those exposed to these emissions on the importance of proper handling of equipment.
Creating optimal soil conditions for crops will also decrease the amount of nitrous oxide
emissions in the atmosphere, along with the exposure to those who work in agriculture.
Considering the contribution of agriculture to nitrous oxide emissions as seen in figure 1 above.
Denitrification of soil should be examined for the mass production of crops to limit worker and
consumer exposure.

References

Alvarez, L., Bricio, C., Blesa, A., Berenguer, J. (2013). Transferable denitrification capability of
thermus thermophilus. Retrieved from
https://www.researchgate.net/figure/The-nitrogen-cycle-Denitrification-consists-of-the-sequentia
l-reduction-of-nitrogen-to_fig1_258060211

Axelsson, G., Ahlborg Jr, G., Bodin, L. (1996). Shift work, nitrous oxide exposure, and
spontaneous abortion among Swedish midwives. Retrieved from
https://oem.bmj.com/content/oemed/53/6/374.full.pdf

Coleman, D. (2019). Implications of MTHFR gene mutations. Retrieved from

https://vanguardhealthandfitness.weebly.com/blog/implications-of-mthfr-gene-mutations

Heijmans, B. T., Gussekloo, J., Kluft, C., Droog, S., Lagaay, A. M., Knook, D. L., … Slagboom,
E. P. (1999). Mortality risk in men is associated with a common mutation in the
methylene-tetrahydrofolate reductase gene (MTHFR). Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed/10196703
 Helen Mendenhall and Miranda Laskey

Nagele, P., Brown, F., Francis, A., Scott, M. G., Gage, B. F., Miller, J. P., & VINO Study Team.
(2014, July). Influence of nitrous oxide anesthesia, B-vitamins, and MTHFR gene
polymorphisms on perioperative cardiac events: the vitamins in nitrous oxide (VINO)
randomized trial. Retrieved from ​https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919550/

Nagele, P., Zeugswetter, B., Wiener, C., Burger, H., Hüpfl, M., Mittlböck, M., & Födinger, M.
(2008, July 1). Influence of Methylenetetrahydrofolate Reductase Gene Polymorphisms on
Homocysteine Concentrations after Nitrous Oxide Anesthesia. Retrieved from
https://anesthesiology.pubs.asahq.org/article.aspx?articleid=1922603

Selzer, R. R., Rosenblatt, D. S., Laxova, R., & Hogan, K. (2003). Adverse Effect of Nitrous
Oxide in a Child with 5,10-Methylenetetrahydrofolate Reductase Deficiency. ​New England
Journal of Medicine​, ​349​(1), 45–50. doi: 10.1056/nejmoa021867

Smith, K.A., Thomson, P.E., Clayton, H., et. al. (1998). Effects if temperature, water content and
nitrogen fertilisation on emissions of nitrous oxide by soils. Retrieved from
https://reader.elsevier.com/reader/sd/pii/S1352231097004925?token=B87F8B6CA5EC4500939
784930E434098F02E5C844F4B09D9DF08A17009C8C35D998DA7CE968F44E717C9425AB9
8CE0BD

Spiro, S. (2012, May 5). Nitrous oxide production and consumption: regulation of gene
expression by gas-sensitive transcription factors. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306620/