Journal Article

Inhibitory effects of soy isoflavones on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-<i>b</i>]pyridine (PhIP)

Atsuya Hikosaka, Makoto Asamoto, Naomi Hokaiwado, Koji Kato, Kazuya Kuzutani, Kenjiro Kohri and Tomoyuki Shirai

in Carcinogenesis

Volume 25, issue 3, pages 381-387
Published in print March 2004 | ISSN: 0143-3334
Published online March 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh031
Inhibitory effects of soy isoflavones on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

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Intake of isoflavones derived from soybean products may impact on prostate cancer risk. Here we evaluated the effects of Fujiflavone, a commercial isoflavone supplement, on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine in cooked meat. F344 male rats were given intragastric administrations of PhIP at the dose of 200 mg/kg twice weekly for 10 weeks. The rats subsequently fed a diet containing 0.25% Fujiflavone showed a significantly lower incidence of prostate carcinomas than those fed a soy-free diet. Interestingly fewer carcinomas but more foci of prostatic intra-epithelial neoplasia (PIN) were observed in the Fujiflavone group although the sum of the two lesions was not altered by Fujiflavone treatment. cDNA array analyses confirmed by semi-quantitative reverse transcription polymerase chain reactions (RT–PCR) revealed Fujiflavone to alter gene expression of ornithine decarboxylase (ODC), prothymosin alpha (PTA) in the rat prostate. No modification of PhIP-induced colon carcinogenesis was evident, except for increased multiplicity of aberrant crypt foci >4 crypts in size. These results indicate that a commercial isoflavone supplement can inhibit PhIP-induced rat prostate carcinogenesis without any adverse effects, possibly by inhibiting progression of PIN to carcinoma, and that down-regulation of ODC and PTA could be related to the underlying mechanisms. Thus, intake of dietary isoflavones can be promising for prevention of human prostate cancer.

Keywords: ACF, aberrant crypt foci; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; ODC, ornithine decarboxylase; PIN, prostatic intra-epithelial neoplasia; PTA, prothymosin alpha

Journal Article.  4391 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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