Tissue-specific induction of sister chromatid exchanges by ehtyl carbamate in mice.
Sister chromatid exchange (SCE) techniques were used to analyze the genetic effects of ethyl carbamate (urethane) in cultured mouse-bone marrow cells, and in several different mouse tissues in vivo. Ethyl carbamate concentrations up to 5.0 mg/ml were ineffective in causing a significant elevation of SCE in vitro. After in vivo drug administration, bone marrow, liver and spermatogonial cells all revealed significant dose-related increases in SCE. Baseline and relative incremental levels of SCE were somatic vs germ tissue-specific. Regenerating liver cells exhibited significantly greater absolute SCE values than all other tissues examined. Marrow cells revealed intermediate values, while germ cells were the least sensitive in SCE responsiveness. Spermatogonia required a fourfold higher dose, over that effective in somatic tissues, to promote an approximate doubling of the baseline SCE level. In vivo SCE analysis affords sensitive risk assessments for different tissues. Thus, this approach; should be generally useful for studying compounds with questionable mutagenic potential, and/or those exerting target organ specificities of related biological activity (eg, toxicity, carcinogenesis).
D000818:Animals; D001711:Biotransformation; D001853:Bone Marrow / Q000187:drug effects; D002478:Cells, Cultured; D003434:Crossing Over, Genetic / Q000187:drug effects*; D008099:Liver / Q000187:drug effects; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051379:Mice; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013093:Spermatogonia / Q000187:drug effects; D014018:Tissue Distribution; D014520:Urethane / Q000494:pharmacology*
D014520:Urethane