Urinary excretion of 3-methyladenine and 1-methylnicotinamide by rats, following administration of [methyl-14C]methyl methanesulphonate and comparison with administration of [14C]methionine or formate.

Following i.p. injection of [methyl-14C]methyl methanesulphonate (MMS) into rats (100 mg/kg) 3-[14C]methyladenine was identified as a urinary product excreted mainly up to 24 h after treatment, the amount over this period being about 0.02 mumol 3-methyladenine. When [14C]MMS and L-[methyl-3H]methionine were injected together no methyl-3H-label was detected in 3-methyladenine, nor was this product detected following injection of [methyl-14C]methionine alone or of [14C]formate. Isotopically labelled 1-methylnicotinamide (1-meNmd) was detected following all the treatments listed, and as previously found by Chu and Lawley, 1-meNmd excretion was enhanced by MMS treatment as judged by increased excretion of 1-[3H]meNmd when [14C]MMS and [3H]methionine were given together. The extent of labelling of 1-meNmd was much lower following injection of [14C] formate, than that from methionine or MMS. The results showed that 3-methyladenine derived only from direct chemical methylation by MMS. They also support the previous suggestion that [methyl-14C]meNmd can result from direct methylation, with a maximal amount of about 3% of excreted meNmd deriving from this route. The possible utility of the methods described for monitoring in vivo alkylation is discussed.