Alteration of cholesterol biosynthetic pathways in the skin of mice administered polycyclic aromatic hydrocarbons

When polycyclic aromatic hydrocarbons were applied solely or together with a tumor promoter (12-O-tetradecanoylphorbol-13-acetate) to the skin of mice, a marked decrease in the level of lathosterol was observed, reflecting a significant change in the metabolism of sterols. Yet the total amount of cholesterol was not changed. When diazacholesterol (a metabolic inhibitor) was administered to mice, both desmosterol and 5 alpha-cholesta-7,24-dien-3 beta-ol accumulated in the skin, whereas the level of lathosterol decreased. These results seem to suggest that a significant portion of lathosterol is formed via 5 alpha-cholesta-7,24-dien-3 beta-ol in addition to the pathway through methostenol. When polycyclic aromatic hydrocarbon was applied to the skin of the mouse treated with diazacholesterol, a significant increase of desmosterol and a marked drop of the level of 5 alpha-cholesta-7,24-dien-3 beta-ol were observed. These results strongly suggest that polycyclic aromatic hydrocarbons perturb the metabolism of sterol in the skin of mice while keeping the total amount of cholesterol unchanged. A similar metabolism also seems to be operating in tumor tissue itself.