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Controlling Factors in Urethan Carcinogenesis in Mice: Effect of Enzyme Inducers and Metabolic Inhibitors

Experimental Pathology Branch, National Cancer Institute, Bethesda, Maryland 20014

The influence of various compounds on pulmonary tumor formation in mice after a single dose of urethan was investigated. Pretreatment by the microsomal enzyme inducers chlordane, phenobarbital, and ß-naphthoflavone reduced the yield of lung tumors, but phenothiazine and diethylaminoethyl diphenyl valerate (SKF-525A) did not. None of these agents by themselves were carcinogenic to the mouse lung in a 16-week test. 3-Methylcholanthrene pretreatment induced lung tumors, the incidence of which was decreased by the subsequent injection of urethan.

Treatment with actinomycin D, puromycin, and cycloheximide, which are expected to affect macromolecular synthesis, gave the same pulmonary tumor incidence after a single dose of urethan as that noted in controls given the vehicle plus urethan.

These data demonstrate that certain enzyme inducers sharply modify the pulmonary tumor yield, but they fail to give a clue to the possible existence of an active metabolite derived from urethan, or the need for macromolecular synthesis in target cells for the operation of the induction process.

Received 10/ 2/70. Accepted 12/23/70.

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