Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Inhibiting the consequences of acrylamide exposure on the male germ line (#183)

Shaun D Roman 1 2 , Aimee L Katen 1 2 , Caitlin G Chambers 1 2
  1. School of Environmental & Life Sciences, The University of Newcastle, Callaghan, NSW, Australia
  2. The Priority Research Centre for Chemical Biology, The University of Newcastle,, Callaghan, NSW, Australia

Humans are chronically exposed to acrylamide, a toxicant present in carbohydrate-rich foods cooked at temperatures above 120°C. Most of the reproductive toxicity associated with acrylamide occurs as a result of its conversion via the enzyme CYP2E1 to glycidamide, an epoxide which forms strong covalent bonds with adenine and guanine. We have successfully built a mouse model of chronic exposure and at human levels of ingestion we see DNA damage in pachytene spermatocytes (Nixon et. al., 2012). Recently we have identified that DNA damage is apparent in the spermatozoa and this damage persists in subsequent generations (Katen et. al., 2016a). We are attempting to inhibit this damage using a CYP2E1 inhibitor. Potential inhibitors are assessed in vitro for the ability to prevent DNA damage in pachytene spermatocytes (Nixon et.al, 2014). Should the inhibitor be effective then we move to our animal models. Initially we examine acute treatment of short duration. If successful we assess inhibitor effectiveness under chronic treatment conditions which better mimic the human situation (Katen et. al., 2016b)

The first inhibitor tested, resveratrol, showed promise as it was a dual purpose inhibitor (Nixon et. al., 2014) as blocked metabolic activity and acted as an anti-oxidant to soak up the free radicals that generate oxidative DNA damage. However, resveratrol has a multitude of targets (Katen & Roman, 2015). When used in a chronic setting resveratrol is capable of premature capacitation of spermatozoa (Katen et. al., 2016b). Therefore new inhibitors need to be tested.

The food processing industry is investing heavily to prevent acrylamide production, our approach is to look downstream. It is worth noting that while our focus is on reproduction another site of CYP2E1 expression is the brain and neurotoxicity is another toxicological site of acrylamide.

 (1) Nixon B.J. et. al., (2012). Toxicological Sciences, 129, 135-145.

(2) Katen A.L. et. al., (2016a) manuscript under review

(3) Nixon B.J. et. al., (2014). PLoS One, 9, e94904

(4) Katen A.L. et. al., (2016b) Reproductive Toxicology 63, 1–12

(5) Katen A. L. & Roman S. D. (2015). Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 777, 91-100.