REACTION OF THE CARCINOGEN DIMETHYLNITROSAMINE WITH NUCLEIC ACIDS IN VIVO

Abstract

The time-sequence of methylation of liver and kidney RNA and DNA after the administration of [C14]dimethylnitrosamine has been investigated. Methylation of liver RNA and kidney RNA reaches a maximum 5-12 hr. after the injection of dimethylnitrosamine, and then decreases, reaching a very low level at 3 weeks. In the liver, where methylation is most extensive, there is a rapid initial rate of loss of methyl group from RNA during the first 2 days, which is not dependent on the concomitant necrosis. Liver DNA and kidney DNA become rapidly methylated; loss of the methyl group occurs rapidly from liver, more slowly from kidney. Rapid incorporation of normal C1 metabolic-pool intermediates takes place into RNA and DNA of liver and kidney; with liver DNA, incorporation continues after the first 24 hr., owing to regeneration of the tissue.