Guanine N7-alkylation in mice in vivo by metrifonate - discussion of possible genotoxic risk in mammals.
Following intraperitoneal administration to male mice (strain AB Jena/Halle) of 14CH3-labelled metrifonate, 22 Ci/mol, in dosages of 0.48, 0.40 and 0.065 mmol/kg, DNA from liver and kidneys was analysed for 14C in N-7 methylguanine (7-MeG). The extent of methylation in liver was found to be maximal at 6 hrs after injection in amounts of 6-8 and 0.8 mumol 7-MeG/mol guanine for the high and the low dose, corresponding to a covalent binding index CBI 4-5. The half-life of excretion of 7-MeG was 5 hrs for the high and 15 hrs for the low dose. The extent of methylation at 0-6 of guanine was estimated to be around 0.002-0.01 mumol 0-6 MeG/mol guanine. Data from references concerning methyl methanesulfonate and dimethyl sulfate are compared with those of metrifonate and the genotoxic response of methylating and non-methylating metabolites is discussed.
D000478:Alkylation; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000378:metabolism; D006147:Guanine / Q000378:metabolism*; D006207:Half-Life; D007700:Kinetics; D008297:Male; D051379:Mice; D009153:Mutagens; D051381:Rats; D012306:Risk; D014236:Trichlorfon / Q000494:pharmacology* / Q000633:toxicity
D009153:Mutagens; D006147:Guanine; D004247:DNA; D014236:Trichlorfon