Chronic Exposure to Acrylamide Induces DNA Damage in Male Germ Cells of Mice

Abstract

Acrylamide is a reproductive toxicant that has been detected in foods such as potato chips and breads. The consequences of chronic exposure to acrylamide in the human diet are unknown; however, rodent experiments have shown that acute acrylamide exposure in males can lead to decreased fertility and dominant lethality. One of the possible mechanisms by which acrylamide elicits these effects is thought to be related to its metabolic conversion to glycidamide, which can form DNA adducts. To determine whether chronic acrylamide exposure produces genetic damage in male germ cells in vivo, male mice were subjected to acrylamide through their drinking water. Acrylamide was administered at 0.001, 0.01, 0.1, 1, and 10 µg/ml for up to 1 year, which was equivalent to 0.0001-2 mg/kg bodyweight/day. At 1, 3, 6, 9, and 12 months, early male germ cells were assessed for DNA damage using a Comet assay modified to detect adducts and γH2A.X expression, a marker of double-strand breaks. Acrylamide treatment did not significantly affect mouse or testis weight, and no gross morphological effects were observed in the testis. However, a significant dose-dependent increase in DNA damage was observed in germ cells following 6 months of exposure in the two highest dosage groups (1 and 10 µg/ml). After 12 months of exposure, increases in damage were detected at doses as low as 0.01 µg/ml (0.001 mg/kg bodyweight/day). The results of this study are the first to demonstrate that chronic exposure to acrylamide, at doses equivalent to human exposures, generates DNA damage in male germ cells of mice.