The effect of nitrogen mustard on the cellular concentrations of nucleic acids in regenerating rat liver.

Numerous publications during the last 6 years have indicated the importance of the nitrogen mustards in clinical and experimental cancer chemotherapy (9, 10, 21, 32, 33, 41, 42). The principal application has been to the treatment of lymphomas and leukemias. Two compounds, methylbis(/3-chloroethyl)amine (HN2) and tris(/3-chloroethyl)amine, have been most widely used. An equally impressive number of investigations have been concerned with some aspect of the mechanism of action of nitrogen mustard. A wide variety of cytotoxic, antimitotic, mutagenic, car cinogenic, and radiomimetic effects have been described (4, 16, 18, 20, 22, 32). From the bio chemical point of view, these findings have led to a consideration of the effects of nitrogen mustard on nucleic acid metabolism. Bodenstein and Kondritzer (3) determined the nucleic acid content of successively older amphibian embryos and found that treatment of the embryos with nitrogen mus tard completely prevented the normal rise of desoxyribonucleic acid (DNA) content with age but failed to affect the corresponding increase of ribonucleic acid (RNA) content. Lowrance and Carter (35) found depressions in the content of RNA and DNA and in the incorporation of P32 into the DNA fraction of bone marrow, spleen, and thymus in rabbits during the early periods after treatment with nitrogen mustard. Skipper et al. (40) demonstrated that the administration of carcinostatic agents, including nitrogen mus tard, to mice reduced the incorporation of formate-C14 into the combined nucleic acid purines of viscera. Goldthwait (23) recently found that HN2 decreased the incorporation of both for-