Studies on liver chromatin RNA from rats treated with alkylating agents

We have examined firstly some properties of rat liver chromatin RNA and nuclear sap RNA and secondly the incorporation of [3H]orotic acid into the RNA in vivo in control rats and in rats treated with the alkylating agents, N,N-dimethylnitrosamine or methyl methane sulphonate. Half or more of the nuclear RNA is associated with the chromatin and consists mainly of two species: one is labelled and probably comprises "nascent" RNA, and the other is unlabelled and of lower molecular weight. Neither species is attributable to cytoplasmic contamination. Studies with added polylysine with RNAase A and with DNAase I suggest that both species are ironically bound to protein and that the labelled species is not associated with the part of the chromatin DNA most readily degraded by DNAase I. After dimethylnitrosamine treatment, the amount of unlabelled RNA remains constant but the amount of labelled RNA increases after a low dose, and decreases after a high dose. After methyl methane sulphonate treatment, no change occurs in either species. These results can be explained by changes in extent of association of the DNA and protein within the chromatin complex.