Sensitivity of Mice to Benzo(a)pyrene Skin Cancer following Acclimation to Cool and Warm Temperature

Abstract

Skin tumorigenesis induced by benzo(a)pyrene (BaP) in male C3H/HeJ mice was accelerated in a cool (T, = 16") and inhibited in a warm (T, = 32") environment, compared to the normal Ta = 23". For example, repetitive, topical application of 0.2 mg BaPlweek in 0.08 toluene resulted in (i) the mean tumor appearance time occurring 4-5 weeks earlier in cool and 2-3 weeks later in warm compared with the 21 -22 weeks average in normal T,; (ii) the average number of tumors per mouse increasing twice as fast in cool as in warm T,; and (iii) shortened survival in cool, lengthened in warm. There were few metastases to internal organs at any temperature. Once initiated, tumors progressed similarly in all Ta's to squamous cell carcinomas. Cool and warm T, per se had little effect on spontaneous tumors, survival, body weight, rectal temperature, or hair growth. However, skin temperature was 1-2" lower in cool and 1-2" higher in warm T, than the normal 32-33'. Physiological adaptation was particularly evident in the 66% average higher food intake in cool and 63% lower in warm T,. These results may help in defining environmental risks in cancer, in increasing the efficiency of cancer screening trials, and in exploring physiological modifiers of carcinogenesis.

Inhibitory Effect of Toluene on Tumor Promotion in Mouse Skin

“…Initiation gen-erally followed within 2-5 days on the clipped back with either benzo[a]pyrene (BaP, Aldrich) or 7,12-dimethylbenz[a]anthracene (DMBA, Sigma), carried in 40 to 80 pl of either acetone or toluene. In some trials, however, 2 weeks of acclimation to cool ( 10-13"C), normal (23"C), or warm (29-3 1 "C) temperature preceded initiation ( 1,2).…”