Effect of chemical carcinogens on cholesterol biosynthetic pathways in the skin of mice.

Abstract:

:The metabolism of zymosterol and mevalonic acid was studied in vitro using the skin homogenates of 3-methylcholanthrene (3MC), diazacholesterol-treated and untreated mice. In normal mouse skin only lathosterol was a major metabolite and the other metabolites, cholesta-5,7,24-trien-3 beta-ol, desmosterol, cholesterol and 7-dehydrocholesterol were much less abundant. However, in the skin homogenate of mice treated with 3MC lathosterol production was depressed, while the production of cholesta-5,7,24-trien-3 beta-ol and desmosterol was significantly increased, the cholesterol level being normal or a little higher. In contrast, in the skin homogenate of mice administered diazacholesterol the production of both lathosterol and cholesterol was almost completely blocked with the slightly increased production of cholesta-5,7,24-trien-3 beta-ol and desmosterol. The metabolism in vitro of [2-14C]-mevalonic acid was quite similar to that of zymosterol, and no additional product which might possibly have been produced by the Kandutsch-Russell pathway was observed. Two pathways for cholesterol biosynthesis, therefore, may exist in mouse skin; the first is lanosterol----zymosterol----5 alpha-cholesta-7,24-dien-3 beta-ol----lathosterol----7-dehydrocholesterol----cholesterol, and the second by Bloch: lanosterol----zymosterol----5 alpha-cholesta-7,24-dien-3 beta-ol----cholesta-5,7,24-trien-3 beta-ol----desmosterol----cholesterol. When mouse skin is treated with 3-MC the former pathway is virtually blocked and the latter is stimulated, keeping the level of cholesterol in the tissue constant or a little higher than normal, which seems to be a significant change in the early stage of chemical carcinogenesis.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Tanimoto Y,Fukao K,Yoshiga K,Takada K,Ohyama Y,Okuda K

doi

10.1093/carcin/11.9.1647

subject

Has Abstract

pub_date

1990-09-01 00:00:00

pages

1647-51

issue

9

eissn

0143-3334

issn

1460-2180

journal_volume

11

pub_type

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