Alkaline elution of rat testicular DNA: detection of DNA strand breaks after in vivo treatment with chemical mutagens.
The alkaline elution technique was used to measure DNA strand breaks in rat testes after intraperitoneal injection of several chemicals known to cause heritable mutations in rodents. Methyl methanesulfonate (MMS), ethyl methanesulfonate, methylnitrosourea, and ethylnitrosourea all produced single strand breaks in rat testicular DNA. For both of these pairs of homologous alkylating agents the relative potency was methyl analog greater than ethyl analog. Strand breaks produced by MMS appeared rapidly (within 2 h) in rat testicular DNA and were partially repaired within 24 h. Studies with low doses of MMS indicate that the assay has the sensitivity to detect DNA strand breaks in the testis after a dose of only 5 mg/kg. Variability in DNA elution profiles for individual control animals and for individual animals given identical doses of MMS was small. In contrast to the results with known mutagens, intraperitoneal injection of nonmutagens such as dimethyl sulfoxide, phenol, and Triton X-15, did not produce strand breaks in testicular DNA. These data indicate that this assay detects DNA strand breaks in the rat testis. The results for several heritable mutagens and nonmutagens are qualitatively predictive of mutagenic activity in the testis.
D000818:Animals; D004277:DNA, Single-Stranded / Q000032:analysis*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005038:Ethylnitrosourea / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D013737:Testis / Q000032:analysis*; D013997:Time Factors
D004277:DNA, Single-Stranded; D009153:Mutagens; D010636:Phenols; D011092:Polyethylene Glycols; D008770:Methylnitrosourea; D004492:Edetic Acid; D005020:Ethyl Methanesulfonate; D008741:Methyl Methanesulfonate; D005038:Ethylnitrosourea; D004121:Dimethyl Sulfoxide