Journal Article

Catechol estrogen metabolites and conjugates in different regions of the prostate of Noble rats treated with 4-hydroxyestradiol: implications for estrogen-induced initiation of prostate cancer

Ercole L. Cavalieri, Prabu Devanesan, Maarten C. Bosland, Alaa F. Badawi and Eleanor G. Rogan

in Carcinogenesis

Volume 23, issue 2, pages 329-333
Published in print February 2002 | ISSN: 0143-3334
Published online February 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.2.329
Catechol estrogen metabolites and conjugates in different regions of the prostate of Noble rats treated with 4-hydroxyestradiol: implications for estrogen-induced initiation of prostate cancer

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Prostate carcinomas arise in 100% of Noble rats treated with estradiol and testosterone. We hypothesize that estrogens initiate prostate cancer mainly by formation of 4-catechol estrogens (CE), followed by their oxidation to catechol estrogen-3,4-quinones (CE-3,4-Q), which can react with DNA. To avoid cancer initiation, CE can be detoxified by catechol-O-methyltransferase (COMT), and CE-3,4-Q by conjugation with glutathione (GSH) or by reduction to CE, catalyzed by quinone reductase and/or cytochrome P450 reductase. To investigate the prostatic metabolism of estrogens, Noble rats were treated with the CE 4-hydroxyestradiol (4-OHE2) or estradiol-3,4-quinone (E2-3,4-Q), and CE metabolites and conjugates were analyzed in the four regions of the prostate, which differ in susceptibility to carcinoma formation. Following treatment of rats with 4-OHE2 (6 μmol/100 g body weight in 200 μl of trioctanoin/dimethylsulfoxide (4:1) by intraperitoneal injection) for 90 min, the non-susceptible ventral (VP) and anterior (AP) prostate had higher levels of 4-methoxyCE and GSH conjugates than the susceptible dorsolateral prostate (DLP) and periurethral prostate (PUP). After treatment with the same molar amount of E2-3,4-Q, the VP and AP contained more GSH conjugates, 4-CE and 4-methoxyCE than the susceptible DLP and PUP. These results suggest that prostate areas susceptible to carcinoma induction have less protection by COMT, GSH, and quinone reductase and/or cytochrome P450 reductase, favoring reaction of CE-3,4-Q with DNA, presumably to initiate cancer.

Keywords: AP, anterior prostate; CE, catechol estrogen(s); CE-Q, catechol estrogen quinone(s); COMT, catechol-O-methyltransferase; CYP, cytochrome P450; Cys, cysteine; DLP, dorsolateral prostate; E1, estrone; E2, estradiol; E2-3,4-Q, estradiol-3,4-quinone; GSH, glutathione; NAcCys, N-acetylcysteine; NBL, Noble; OHE2, hydroxyestradiol; PUP, periurethral prostate; -SG, glutathione moiety; VP, ventral prostate

Journal Article.  3210 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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