GLUTATHIONE DEPLETION POTENTIATES ETHYL METHANESULFONATE-INDUCED DAMAGE TO SPERM CHROMATIN STRUCTURE

Male rats were treated with phorone at dosages previously shown to red uce glutathione in rodent reproductive tracts, followed by a single ch allenge with ethyl methanesulfonate, a known mutagenic and clastogenic agent. Epididymal sperm collected 8 and 15 days after exposure from p horone pretreated animals had a significantly greater alteration of sp erm chromatin structure, defined as an increased susceptibility to DNA denaturation in situ, relative to sperm obtained from animals injecte d with saline alone or saline + EMS (50, 100, 150, or 200 mg/kg bw). T hese data support the hypothesis that ethyl methanesulfonate-induced a lkylation of developing sperm chromatin protamines causes a significan t 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 d ominant lethal mutations.