In vitro synthesis of 16 alpha-hydroxyestrone by female rat liver microsomes: its possible role in the etiology of breast cancer.
Liver homogenates from female rat strains (Sprague-Dawley, Wistar and Fisher) were incubated in a NADPH regenerating medium in the presence of labelled and unlabelled estrone. Liver microsomes isolated from male rats and female mice were used as positive controls. Using HPLC and paper chromatography, under the experimental conditions used it was found that liver homogenates from female rats were able to convert estrone to various metabolites such as 16 alpha-hydroxyestrone. In a mutagenicity assay (Ames test), with 16 alpha-hydroxyesterone as test substance, two strains (TA98 and TA1538) of the five strains tested showed a 2-3-fold increase in the number of his+ revertants relative to the control values. Estrone did not cause any mutagens in the test used. It is concluded that female rats are able to synthesize 16 alpha-hydroxyestron in vitro. Whether this compound is risk factor for breast cancer remains unclear.
Arts
C J
CJ
TNO-CIVO Toxicology and Nutrition Institute, Department of Clinical Biochemistry, Zeist, The Netherlands.
Wilmer
J W
JW
de Bie
A T
AT
van den Berg
H
H
D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology*; D002851:Chromatography, High Pressure Liquid; D004970:Estrone / Q000494:pharmacology; D005260:Female; D006894:Hydroxyestrones / Q000096:biosynthesis* / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains
D006894:Hydroxyestrones; C026702:16-hydroxyestrone; D004970:Estrone