The Effect of 3-Methylcholanthrene on Postlanosterol Cholesterol Biosynthetic Pathways in Mouse Skin

Abstract

Repeated topical application of 3-methylcholanthrene to the backs of BALB/c mice lowered the tissue levels of lathosterol and provitamin D₃, intermediates in one of the cholesterol biosynthetic pathways (the Δ⁷ pathway), though the activities of lathosterol 5-desaturase and provitamin D₃ 7-reductase were similar to those of control animals. These results seemed to indicate that carcinogen treatment exerted a depressive effect at some earlier step(s) than lathosterol synthesis. However, the content of cholesterol in mouse skin was not lowered in these animals, suggesting that another biosynthetic pathway might be activated. When diazacholesterol, which is known to inhibit the conversion of desmosterol to cholesterol, was administered together with the carcinogen, a marked accumulation of desmosterol was observed compared to animals given only diazacholesterol. Since desmosterol is an intermediate in the pathway in which the Δ²⁴ double bond is reduced at the final step (the Δ²⁴ pathway), this seemed to suggest that the Δ²⁴ pathway was activated by carcinogen treatment.