The effect of deuterium substitution on carcinogenesis by azoxymethane

Azoxymethane was synthesized labeled with deuterium in one or other of the two methyl groups. Groups of 20 male F344 rats were given either 4 mg or 1 mg per week of each of the labeled compounds or of unlabeled azoxymethane each week in drinking water, for 30 weeks, after which the animals were kept until they died. All in the high dose groups died earlier with tumors induced by the treatment than did those in the low dose groups. Azoxymethane itself led to earlier death than either of the deuterium-labeled compounds, and methylazoxymethane-d3 seemed to be the least potent compound. The incidence of liver tumors and of kidney tumors was similar in the groups receiving the same dose of all 3 compounds. However, there were fewer tumors of the colon in animals given methyl-d3-azoxymethane than with the other 2 compounds. These results are consistent with the concept that either methyl group of azoxymethane can be oxidized in the course of activation to a proximate carcinogenic agent for liver, kidney or colon of rats, but that oxidation of the methyl group next to the nitrogen bearing oxygen is more important in the induction of colon tumors.