Resveratrol treatment reduces acrylamide-induced DNA damage in male germ cells (#37)
Acrylamide is a neurotoxin in rodents and humans and a genotoxin, carcinogen and reproductive toxin in rodents. Acrylamide is used as an additive in the cosmetics and paper industries and is produced from asparagine during the high temperature cooking of many starch-rich foods. Therefore, humans are continuously exposed to low doses of acrylamide.
We established a mouse model for the study of chronic acrylamide exposure in males (1) and demonstrated that acrylamide causes DNA damage in male germ cells at estimated human exposure levels. There are a number of ways that acrylamide can cause DNA damage in cells. Significantly glycidamide, the metabolite of acrylamide, is highly reactive and forms adducts with DNA. Glycidamide is formed by oxidation of acrylamide via the cytochrome P450 enzyme Cyp2e1. Resveratrol can act as an antioxidant via direct free radical scavenging and has also been shown to act as a non-competitive inhibitor of Cyp2e1, preventing glycidamide formation.
The current study examined the capacity of resveratrol to inhibit DNA damage in germ cells caused by chronic acrylamide exposure. Mice were treated with resveratrol, via an intraperitoneal injection once per week, for six months in the presence or absence of 1µg/ml acrylamide in the drinking water. Early germ cells were isolated and assessed for DNA damage using the Comet assay. Once again acrylamide treatment was found to induce DNA damage. Resveratrol treatment reduced the levels of DNA damage. DNA damage was also assessed by the expression of the protein gamma-H2AX, a marker of double strand break repair. Acrylamide treatment led to increased gamma-H2AX expression in germ cells, which was reduced in resveratrol treated mice.
The results of the present study confirm that chronic, low dose acrylamide exposure induces DNA damage during spermatogenesis. It has also established the potential of resveratrol to reduce this DNA damage.
- Nixon, B. J., Stanger, S. J., Nixon, B. and Roman, S. D. (2012). Chronic exposure to acrylamide induces DNA damage in male germ cells of mice. Toxicol Sci 129, 135-145.