Interaction of the carcinogen 3,3-dimethyl-1-phenyltriazene with nucleic acids of various rat tissues and the effect of a protein-free diet.

The methylation by 3,3-[14C]dimethyl-1-phenyltriazene of nucleic acids in various rat tissues was investigated. Following a single s.c. injection of 3,3-[14C]dimethyl-1-phenyltriazene (50 mg/kg), approximately 40% of the radioactivity was subsequently exhaled as 14CO2. Expiration of 14CO2, metabolic 14C labeling of liver proteins, and formation of 7-[14C]methylguanine, the major reaction product with nucleic acid bases, were completed within about 15 hr. Minor alkylation products detectable in DNA were O6-methylguanine and 3-methyladenine. In cytoplasmic RNA, 1-methyladenosine, 3-methylcytidine, and O6-methylguanosine were present in addition to 7-methylguanosine. Concentrations of 7-methylguanine were highest in nucleic acids of kidney and liver. Among the other organs investigated (brain, lung, spleen, small intestine), 7-methylguanine levels showed little variation but were 4 to 7 times lower than those in liver and kidney. Feeding of a protein-free diet prior to 3,3-[14C]dimethyl-1-phenyltriazene administration reduced the formation of 7-methylguanine in liver and kidney RNA, whereas in the remaining organs the extent of methylation was markedly increased. The results are discussed with respect to the significance of methylation at specific sites in nucleic acids for the initiation of malignant transformation and the possible role of 3-methyl-1-phenyltriazene as the systemically distributed proximate carcinogen of 3,3-dimethyl-1-phenyltriazene.