Mutagenicity of the human carcinogen treosulphan, and its hydrolysis product, dl-1,2:3,4-diepoxybutane in mammalian cells.
The cytotoxicity and mutagenicity of the human carcinogen, treosulphan, and its hydrolysis product, dl-1,2:3,4-diepoxybutane (DEB), were studied in Chinese hamster ovary, AS52, cells. Treosulphan (0.1-1.0 mM) is toxic and mutagenic at the gpt locus. A strong pH dependence was noted. DEB is cytotoxic and mutagenic at a much lower dose (0.025 mM), but these effects were not affected by pH. The results suggest that the toxic and mutagenic effects of treosulphan are mediated by its hydrolysis product DEB, and that the conversion of treosulphan to DEB is highly pH-dependent.
Zhu
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S
Experimental Carcinogenesis and Mutagenesis Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Zeiger
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E
D000704:Analysis of Variance; D000818:Animals; D002066:Busulfan / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D013997:Time Factors
D004852:Epoxy Compounds; D009153:Mutagens; C007366:diepoxybutane; C018404:treosulfan; D002066:Busulfan