Cross-linking of DNA by alkylating agents and effects on DNA function in the chick embryo.

Drug-induced cross-links are found in the DNA of chick embryos within 6 hr after injection of mitomycin C and methyl-di-(2-chloroethyl)amine into the egg and 24 hr after injection of triethylene thiophosphoramide. Effects on the rates of synthesis of DNA, RNA, and protein were studied with chemical assays for total content of these macromolecules as well as radioactive precursor incorporation. All three drugs inhibited DNA synthesis before RNA and protein synthesis were affected, but there were discrepancies between the two methods of measuring macromolecular synthesis; thus, radioactive precursor incorporation is not always a reliable measurement of macromolecular synthesis in the chick embryo. When the effects of methyl-di-(2-chloroethyl)amine were compared to those of dimethyl-2-chloroethylamine, a monofunctional analog, the former was a more effective inhibitor of DNA and RNA synthesis at equivalent alkylating doses; however, the fact that the monofunctional analog had some inhibitory activity suggests that not all the effects of difunctional alkylating agents are due to their DNA cross-linking activity.