In vivo distribution of dimethylnitrosamine metabolites in mouse liver and their binding to micrococcal nuclease sensitive and resistant chromatin

Abstract

Mice were injected i.p. with a single dose (5 mg/kg body wt) of [14C]dimethylnitrosamine and killed at time intervals between 15 and 120 min. Isolated nuclei were incubated with micrococcal nuclease and the chromatin separated into a 1100 g pellet P1 and supernatant fraction S1. The incorporation of 14C from [14C]dimethylnitrosamine into chromatin was significantly higher in the P1 than the S1 fraction. The purine bases of the P1 DNA showed a lower methylation than those of the S1 DNA. In contrast, radioactivity of the proteins was higher in the P1 than the S1 fraction. It is concluded that the open structures of the S1 chromatin were preferentially attacked by the hepatotoxin leading to a high 14C-labelling of the DNA relative to that of the proteins.