Absence of unscheduled DNA synthesis in rat hepatocytes treated with mutagenic and cytotoxic chlorinated humic substances.
Chlorinated hydrophilic macromolecular humic acids (CHMA) (0.07-3.0 mg per plate) were mutagenic in Salmonella typhimurium strain TA100. In contrast, the chlorinated derivatives did not induce unscheduled DNA synthesis (nuclear incorporation of [3H]thymidine) in cultured rat hepatocytes even after depletion of intracellular glutathione with buthionine sulphoximine (0.001 mM) and at concentrations of CHMA up to 3.0 mg per plate eliciting cytotoxicity. Glutathione depletion did however potentiate cytotoxicity and hepatocyte glutathione concentrations were lowered by CHMA treatment indicating reactivity of CHMA in the cell.
Ubom
G
G
School of Biochemistry, University of Birmingham, Edgbaston, UK.
Chipman
J K
JK
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage; D004260:DNA Repair; D005978:Glutathione / Q000378:metabolism; D006812:Humic Substances / Q000378:metabolism / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity
D006812:Humic Substances; D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; D014874:Water Pollutants, Chemical; D004247:DNA; D005978:Glutathione