title: Chronic acrylamide exposure in male mice induces DNA damage to spermatozoa; Potential for amelioration by resveratrol.
abstract: Humans are chronically exposed to acrylamide since carbohydrate rich foods contain the toxicant as a result of cooking at high temperatures. While acrylamide is unreactive with DNA, it is readily oxidised to glycidamide, which adducts with DNA. This metabolism occurs via the enzyme, cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1). Acrylamide was administered to male CD1 mice for three or six months at a dose of 0.18mg/kg bodyweight/day. DNA damage was detected in germ cells and mature spermatozoa of exposed mice without compromising their overall fertility. The use of resveratrol, an antioxidant and known CYP2E1 inhibitor, was found to ameliorate the DNA damage in both germ cells and spermatozoa. However, extended resveratrol treatment (six months, 10.0mg/kg bw/week) resulted in premature activation of these cells. Thus the DNA damage found in spermatozoa after chronic acrylamide administration can be alleviated but an alternative CYP2E1 inhibitor may be required.
authors.affiliation: Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia; The Priority Research Centres for Reproductive Sciences and Chemical Biology, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Katen
authors.affiliation: Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia; The Priority Research Centres for Reproductive Sciences and Chemical Biology, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Simone J
authors.initials: SJ
authors.lastname: Stanger
authors.affiliation: Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia; The Priority Research Centres for Reproductive Sciences and Chemical Biology, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Anderson
authors.affiliation: Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia; The Priority Research Centres for Reproductive Sciences and Chemical Biology, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Nixon
authors.affiliation: Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia; The Priority Research Centres for Reproductive Sciences and Chemical Biology, University of Newcastle, Callaghan, New South Wales 2308, Australia. Electronic address: shaun.roman@newcastle.edu.au.
authors.forename: Shaun D
authors.initials: SD
authors.lastname: Roman
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D020552:Comet Assay; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D065691:Cytochrome P-450 CYP2E1 Inhibitors / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D008297:Male; D051379:Mice; D000077185:Resveratrol; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000975:Antioxidants; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D013267:Stilbenes; D020106:Acrylamide; D014443:Tyrosine; D019392:Cytochrome P-450 CYP2E1; C000617651:cytochrome P-450 2E1, mouse; D000077185:Resveratrol
keywords: Acrylamide; CYP2E1; DNA damage; Glycidamide; Resveratrol; Spermatozoa