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.
Fukao
K
K
Department of Oral and Maxillofacial Surgery I, Hiroshima University, School of Dentistry, Japan.
Tanimoto
Y
Y
Kayata
Y
Y
Yoshiga
K
K
Takada
K
K
Ohyama
Y
Y
Okuda
K
K
D000818:Animals; D001373:Azacosterol / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis*; D008297:Male; D013058:Mass Spectrometry; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012878:Skin Neoplasms / Q000032:analysis; D013261:Sterols / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D011083:Polycyclic Compounds; D013261:Sterols; D008748:Methylcholanthrene; D002784:Cholesterol; D001373:Azacosterol; D013755:Tetradecanoylphorbol Acetate