Interaction of the Carcinogen 3,3-Dimethyl- l -phenyltr iazene with Nucleic Acids of Various Rat Tissues and the Effect of a Protein-free Diet 1

The methylation by 3,3-[~4C]dimethyl-l-phenyltriazene of nucleic acids in various rat tissues was investigated. Following a single s.c. injection of 3,3-['4C]dimethyl-l-phenyl triazene (50 mg/kg), approximately 40% of the radioactivity was subsequently exhaled as ~4CO2. Expiration of '4CO2, metabolic ]4C labeling of liver proteins, and formation of 7[~4C]methylguanine, the major reaction product with nucleic acid bases, were completed within about 15 hr. Minor alkylation products detectable in DNA were O"-methylguanine and 3-methyladenine. In cytoplasmic RNA, 1-methyladenosine, 3-methylcytidine, and O"-methylguanosine were present in addit ion to 7-methylguanosine. Concentrations of 7methylguanine 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[ '4C]dimethyl-l-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 mal ignant transformation and the possible role of 3-methyl-l-phenyltr iazene as the systemically distributed proximate carcinogen of 3,3-dimethyl-l-phenyltriazene.