Activity of organophosphorus insecticides in bacterial tests for mutagenicity and DNA repair--direct alkylation vs. metabolic activation and breakdown. I. Butonate, vinylbutonate, trichlorfon, dichlorvos, demethyl dichlorvos and demethyl vinylbutonate.
The following organophosphates were tested for their ability to induce DNA damage in a rec-type repair test with Proteus mirabilis strains PG713 (rec- hcr-) and PG273 (wild type) and point mutations in his- strain TA100 of Salmonella typhimurium--butonate: O,O-dimethyl-(1-n-butyryloxy-2,2,2-trichloroethyl)-phosphonate; vinylbutonate: O,O-dimethyl-(n-butyryloxy-2,2-dichlorovinyl)-phosphonate; trichlorfon: O,O-dimethyl-(1-hydroxy-2,2,2-trichloroethyl)-phosphonate; dichlorvos: O,O-dimethyl-O-(2,2-dichlorovinyl)-phosphate; the demethylated derivatives--demethyldichlorvos: O-methyl-O-(2,2-dichlorovinyl)-phosphoric acid; demethyl vinylbutonate: O-methyl-(1-n-butyryloxy-2,2-dichlorovinyl)phosphonic acid. Of the six compounds tested, dichlorvos and trichlorfon induced base pair substitutions and DNA damage. No mutagenicity and DNA damage were found in experiments with butonate, vinylbutonate, demethyl vinylbutonate and demethyl dichlorvos. Genotoxic activity for dichlorvos and the absence of both mutagenic and RNA damaging properties for its non-alkylating demethyl derivative favors the hypothesis that alkylation of DNA is the essential step for mutation induction by this organophosphate. Furthermore, the absence of genetic effects after treatment with vinylbutonate and demethyl dichlorvos does not support a crucial role of vinyl or allyl groups in side chains of organophosphates for genetic activity. Microsomal enzymes decreased genetic activity of dichlorvos and trichlorfon in vitro. No evidence for a role of metabolic activation in the mutagenic activity of any of these compounds was found.
D000477:Alkylating Agents; D001711:Biotransformation / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D004006:Dichlorvos / Q000031:analogs & derivatives / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000633:toxicity; D014236:Trichlorfon / Q000633:toxicity
D000477:Alkylating Agents; D007306:Insecticides; D009153:Mutagens; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C006845:butonate; C028080:vinylbutonate; C034560:demethylvinylbutonate; D004006:Dichlorvos; D014236:Trichlorfon; C020718:caviphos