Relation of thymidine index to pulmonary tumor response in mice receiving urethan and other carcinogens.

In strain A mice, urethan, 1 mg/gm body weight, produces a decrease in the thymidine index of the lung within 1 day, with recovery and rebound by 7 days. These events are not seen with 0.25 mg/gm urethan although this dose also produces pulmonary tumors in 100% of strain A mice. The initial decrease in the thymidine index is seen also with 3-methylcholanthrene and nitrogen mustard, with the nadir at 3 days. Inhibition at 1 day occurs also in strains C3H and C57BL following 1 mg/gm urethan, but the rebound is less than in strain A. Urethan inhibition of labeled cells is accentuated by actinomycin D, cytosine arabinoside, and puromycin; pulmonary carcinogenesis is also slightly inhibited. It is suggested that the inhibition of DNA synthesis, as manifested by the thymidine index, may represent a toxic side effect rather than a key event in carcinogenesis.

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