Early Differential Effects of 3-Methylcholanthrene and Its “K-Region” Epoxideon Mouse Skin. Possible Implication in the Two-Stage Mechanism of Tumorigenesis2

Abstract

Repeated percutaneous coadministration of 1.5 μmoles 1,1,I-trichloro-2-propene oxide (TCPO) with 1.5-3 μmoles 3-methylcholanthrene (MCA) increased the carcinogenic effect of the polycyclic hydrocarbon on mouse skin, presumably by inhibition of the hydration of MCA-ll,12-oxide, which would increase the effective intracellular concentration of the carcinogenic epoxide. A single administration of TCPO also increased the tumor incidence and shortened the latency period in experiments where MCA was the initiator and phorbol ester, the promotor. Topically applied MCA-11,12-oxide after either single or repeated administration with or without TCPO was only weakly tumorigenic on mouse skin, as compared to the parent MCA. Measured morphometrically and cytokinetically, the epidermal hypertrophy and hyperplasia seen after MCA treatment were absent after application of the 11,12-oxide. The oxide, on the other hand, caused a thinning of intrafollicular epidermis due to a decrease in total number of epithelial cells.