A comparative study of guanine N7-alkylation in mice in vivo by the organophosphorus insecticides trichlorphon, dimethoate, phosmet and bromophos.
Following intraperitoneal administration to male mice (strain AB Jena/Halle) of 14C-methyl-labelled trichlorphon, dimethoate, phosmet and bromophos, 10-20 Ci/mol, in dosages of 0.06-0.55 mmol/kg, DNA from liver and kidneys was analyzed for 14C in N-7 methylguanine (7-MeG). The extents of methylation were in the range of 5-10 mumol 7-MeG/mol guanine for trichlorphon and dimethoate and of 0.2-0.4 for phosmet and bromophos, for high doses, respectively Excretion half-lives of 7-MeG were differing between trichlorphon (5 hrs, high dose, and 15-17 hrs, low dose) and dimethoate (23-160 hrs, high dose). The extents of methylation at 0-6 of guanine were estimated to be around 0.01 mumol 0-6 MeG/mol guanine for high doses of organophosphates of sufficient water solubility. Factors associated with the partition of organophosphates in mammalian systems are useful for estimating DNA attack by organophosphates in mammals in vivo.
D000478:Alkylation; D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D004247:DNA / Q000032:analysis; D004117:Dimethoate / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007306:Insecticides / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008745:Methylation; D051379:Mice; D063086:Organothiophosphates / Q000494:pharmacology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D010706:Phosmet / Q000494:pharmacology*; D014236:Trichlorfon / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D007306:Insecticides; D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D006147:Guanine; C008450:7-methylguanine; C100092:bromophos; D004247:DNA; D014236:Trichlorfon; D010706:Phosmet; D004117:Dimethoate