Methylation of Ribonucleic Acids of Liver and Other Organs in Different Species Treated With C14- and H3-Dimethylnitrosamines In Vivo23

Abstract

When the carcinogen dimethylnitrosamine, labeled with radioactive carbon (C¹⁴-DMN), was injected into rats, mice, hamsters, and guinea pigs in doses sufficient to cause acute hepatic necrosis, radioactivity was found in the ribonucleic acid (RNA) of liver, kidney, spleen, and pancreas. Incorporation was greatest in liver and least in pancreas, with intermediate values in kidney and spleen that showed some species differences. Ion-exchange Chromatographic profiles of hydrolysates of the labeled liver RNA's confirmed previous work with the rat and showed similar patterns in the other species, which indicated that most of the radioactivity was present as 7-methylguanine and suggested that methylation of the RNA's had occurred in vivo. Tritiated dimethylnitrosamine (H³-DMN) was prepared by the Wilzbach exchange reaction, and its metabolic fate was compared with that of C¹⁴-DMN in rats and mice. The tritium was also incorporated into the RNA's of liver and other organs in both species, the distribution showing some similarities to and some dissimilarities to that observed with C¹⁴-DMN. Comparison of the ion-exchange Chromatographic profiles of hydrolysates of the labeled RNA's from different organs confirmed that incorporation probably occurs by two processes: 1) via normal “one-carbon” metabolic intermediates; 2) by methylation of the nucleic acids. Incorporation via normal intermediates was higher from C¹⁴-DMN than from H³-DMN. Calculations of the degree of methylation of the RNA's of different organs in rat and mouse were made. In both species the liver showed the highest degree of methylation, with the next highest in the kidney of the rat and lung of the mouse; the other organs showed low values. These results are discussed in relation to incidence and distribution of tumors in the different species and organs.