The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

The consequences of multigenerational exposure to acrylamide on DNA damage in the male germ line (#55)

Caitlin G Chambers 1 2 3 , Aimee L Katen 1 2 3 , Brett Nixon 1 2 , Shaun D Roman 1 2 3
  1. Discipline of Biology, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia
  2. The Priority Research Centre for Reproductive Biology, University of Newcastle, Callaghan, New South Wales, Australia
  3. The Priority Research Centre for Drug Development, University of Newcastle, Callaghan, New South Wales, Australia

Humans are chronically exposed to acrylamide in carbohydrate-rich foods cooked above 120°C. CYP2E1, an enzyme found within testes and epididymides, solely converts acrylamide to glycidamide. Alone CYP2E1 leaks reactive oxygen species leading to oxidative DNA damage, whereas in the presence of acrylamide the resulting glycidamide directly adducts to the DNA.

We have previously demonstrated chronic acrylamide administration to male mice, at a human relevant dose (1 µg/mL drinking water for 6 months (M)) increased DNA damage in mature spermatozoa and led to induction of the CYP2E1 protein within spermatocytes [1]. Notably, CYP2E1 induction also occurred in the testes of unexposed offspring of acrylamide-exposed fathers where it too was associated with an increase in oxidative DNA damage [1]. This raises concerns for increased susceptibility of offspring to acrylamide-induced DNA damage. To explore this possibility, we are currently exposing the male offspring of acrylamide-exposed fathers using a shorter treatment regimen (3M at 1 µg/mL) and extending the study to the F2 generation. We report here on the F0 and F1 generations. Our shorter exposure regimen increased DNA damage in spermatozoa of acrylamide-exposed F0 males (127% of control). Similarly, this shorter exposure increased DNA damage in spermatozoa of the F1 generation. As with the longer exposure, unexposed male offspring had increased DNA damage in their spermatozoa (115% of control, n=14-17 representing n=4 F0). Surprisingly, we found significantly higher DNA damage in spermatozoa of the unexposed F1 generation than that of their directly exposed (1 µg/mL for 3M) littermates. This suggests an increased level of CYP2E1 resulting from paternal acrylamide exposure preferentially generates increased DNA damage in the absence of the substrate.

This study demonstrates that a paternal acrylamide exposure regimen briefer than previously investigated has a detrimental effect on the offspring and their genetic potential with, or without, further exposure to acrylamide.

  1. 1. Katen AL, Chambers CG, Nixon B, Roman SD. Chronic acrylamide exposure in male mice results in elevated DNA damage in the germline and heritable induction of CYP2E1 in the testes. Biol Reprod. 2016;95(4):Article 86, 1-15.