Methylation of purines and nicotinamide in the rat by dichlorvos.

Dichlorvos (dimethyl 2,2-dichlorovinyl phos­ phate) is a methylating compound 1 and it has been shown to methylate nucleic acid in vitro 2’ 3 and in bacteria3’ 4 as well as to yield 7-methylguanine in mice following i.p. injection and inhalation ex­ posure 4. In the present study two male R strain rats (240 and 260 g, 3 1/2 months old) were given 225 /<Ci of [14C-methyl]-dichlorvos (3.2 mCi/mmol 4) by i.p. injection. The animals were then placed in a meta­ bolic cage with free access to food and water. Urine wras collected for four consecutive 24 h periods during which resp. 53, 4.1, 1.2, and 0.7 per cent of the administered radioactivity was excreted by this route. Analysis of the urinary excretion of 1-methyl­ nicotinamide during the first 24 h period by the procedure given by Chu and Lawley 5 showed that 1.8 nCi was excreted as such. This indicates that dichlorvos behaves as methyl methanesulfonate which also yields 1-methylnicotinamide5. Urinary purines were isolated and chromato­ graphed on a Dowex 50-X12 column with gradient hydrochloric acid and the radioactivity assayed as described previously4. The amounts of 7-methyl­ guanine (7-meG) and 3-methyladenine (3-meA), which elute together in the system used, were resp. 5.8, 3.9, 2.8, and 1.9 nCi for the four 24 h periods. The relative amounts of 7-meG and 3-meA in the three first periods were determined by paper chro­ matographic separation as described by Löfroth et