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.