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Effects of Uracil Mustard on DNA, RNA, and Protein Biosynthesis in Tissues of A/J Mice

National Cancer Institute, NIH, Bethesda, Maryland 20014

The effects of 5-bis(2-chloroethyl)aminouracil (uracil mustard) on some of the biochemical events occurring in lung were studied since this compound, a reactive alkylating agent and analog of uracil, markedly increased the incidence and number of lung tumors in strain A/J mice. Similar measurements were performed in kidney and liver, organs which do not undergo a tumorigenic response to uracil mustard, and were compared to the effects of uracil mustard in lung.

The in vivo incorporation of several nucleic acid precursors into macromolecular components in the cell was studied as a function of drug administration. Incorporation of thymidine-³H into DNA, of uridine-³H into total RNA, and of orotic acid-³H into nuclear RNA of lung, liver, and kidney was inhibited by the drug. Incorporation of L-leucine-¹⁴C into protein was slightly inhibited immediately after administration of uracil mustard followed by a marked stimulation in liver and kidney. The possible relationships of these alterations to the carcinogenic response are discussed in view of current concepts of cellular activity and macromolecular function.

Received 9/ 2/66. Accepted 2/16/67.