Cellular injury and carcinogenesis. Alkylation of ribonucleic acid of rat liver by diethylnitrosamine and n-butylmethylnitrosamine in vivo

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Abstract
Rats are injected intraperitoneally with the hepatotoxic carcinogens diethylnitrosamine and n-butylmethylnitrosamine and with tert-butylmethylnitrosamine, which has low hepatoxicity. The nitrosamines are labeled in various positions with radioactive carbon. The dose, with the more toxic compounds, was adequate to cause acute necrosis of the liver. The labeled RNA from the liver of rats treated with the methyl-labeled isomers was hydrolysed with acid and analysed by chromatography and ultraviolet spectroscopy. After treatment of the rats with tert-butylmethylnitrosamine, the radio-activity of the liver RNA was nearly all in major normal components and no 7-methylguanine was detected. The time-course of incorporation of radioactivity from labeled diethylnitrosamine was studied and maximal in RNA and proteins of rat liver and kidney 24 hr. after injection. Acid hydrolysis of the labelled RNA from rats injected with [C14] diethylnitrosamine, followed by chromatography and ultraviolet spectroscopy, showed the presence of 7-ethylguanine in the hydrolysate. These results further support the hypothesis that the dialkylnitrosamines owe some of their biological actions to the metabolic production of alkylating agents in the cells of susceptible organs. Possible similarities between the mechanisms of chemical carcinogenesis and mutagenesis by nitrosamines are discussed.