Measurement of 7-Methylguanine as an Estimate of the Amount of Dimethylnitrosamine Formed following Administration of Aminopyrine and Nitrite to Rats¹

We have demonstrated that there is a dose-related increase in the excretion of 7-[methyl-¹⁴C]methylguanine ([¹⁴C]m⁷Gua) following p.o. administration of di[methyl-¹⁴C]methylnitrosamine to rats. Urine was collected for 24 hr after di[methyl-¹⁴C]methylnitrosamine administration, and the purines were precipitated from an aliquot of the urine with silver nitrate. Purines were released from the precipitate with HCI, and [¹⁴C]m⁷Gua was quantified by chromatography on an Aminex A-6 column. The excretion of [¹⁴C]m⁷Gua increased linearly with the dose of dimethylnitrosamine. This relationship was used to estimate the amount of di[methyl-¹⁴C]methylnitrosamine formed in the reaction of [¹⁴C]aminopyrine with sodium nitrite in rats gavaged with these compounds. The dose of dimethylnitrosamine was also estimated from the amount of alkylation of liver DNA in the same animals. These estimates usually differed by less than a factor of 2. [¹⁴C]m⁷Gua could be detected in urine when very low doses of [¹⁴C]aminopyrine and sodium nitrite were administered. The possibility of using this assay to obtain data on nitrosation in humans is discussed.