9,10-Dihydroxy-9,10-dihydro-3-methylcholanthrene-2-one: a principal metabolite of the potent carcinogen 3-methylcholanthrene-2-one by rat liver microsomes.
A principal metabolite, formed in the metabolism of the potent carcinogen 3-methylcholanthrene-2-one (3MC-2-one) by liver microsomes from either untreated, or phenobarbital-treated or 3-methylcholanthrene (3MC)-treated rats, was isolated by reversed-phase HPLC. This metabolite has been identified as a 9,10-dihydrodiol with a (9R,10R):(9S,10S) enantiomer ratio of approximately 84:16 by all three rat liver microsomal preparations. The 9,10-dihydrodiol metabolite and its NaBH4 reduction products [a pair of diastereomeric 9,10-dihydroxy-9, 10-dihydro-2-OH-3MC (2-OH-3MC 9,10-dihydrodiols)] were characterized by UV-visible absorption, mass, and circular dichroic spectral, and chiral stationary phase HPLC analyses. Identification of 9,10-dihydroxy-9,10-dihydro-3MC-2-one (3MC-2-one 9,10-dihydrodiol) as the predominant metabolite of the potent carcinogen 3MC-2-one suggests that 3MC-2-one may be metabolically activated to a bay region 9,10-diol-7,8-epoxide, similar to the previously established metabolic activation pathways of 3MC and 1-hydroxy-3-methylcholanthrene (1-OH-3MC).
Shou
M
M
Department of Pharmacology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Yang
S K
SK
D000818:Animals; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004790:Enzyme Induction; D008297:Male; D008748:Methylcholanthrene / Q000302:isolation & purification / Q000378:metabolism* / Q000031:analogs & derivatives; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
C063713:9,10-dihydroxy-9,10-dihydro-3-methylcholanthrene-2-one; C063712:3-methylcholanthrene-2-one; D008748:Methylcholanthrene