Glutathione depletion potentiates ethyl methanesulfonate-induced damage to sperm chromatin structure.
Male rats were treated with phorone at dosages previously shown to reduce glutathione in rodent reproductive tracts, followed by a single challenge with ethyl methanesulfonate, a known mutagenic and clastogenic agent. Epididymal sperm collected 8 and 15 days after exposure from phorone pretreated animals had a significantly greater alteration of sperm chromatin structure, defined as an increased susceptibility to DNA denaturation in situ, relative to sperm obtained from animals injected with saline alone or saline+EMS (50, 100, 150, or 200 mg/kg bw). These data support the hypothesis that ethyl methanesulfonate-induced alkylation of developing sperm chromatin protamines causes a significant stress on chromatin structure leading to increased DNA damage. This is the first report showing that glutathione depletion potentiates EMS-induced chromatin structural alterations that are likely related to dominant lethal mutations.
Evenson
D P
DP
Olson Biochemistry Laboratories, Department of Chemistry, South Dakota State University, Brookings.
Jost
L K
LK
Gandy
J
J
D000818:Animals; D002843:Chromatin / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000633:toxicity*; D005978:Glutathione / Q000502:physiology*; D007659:Ketones / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000187:drug effects* / Q000648:ultrastructure
D002843:Chromatin; D007659:Ketones; C018637:phorone; D005020:Ethyl Methanesulfonate; D005978:Glutathione