Journal Article

An acyclic retinoid, NIK-333, inhibits <i>N</i>-diethylnitrosamine-induced rat hepatocarcinogenesis through suppression of TGF-α expression and cell proliferation

Masataka Kagawa, Tetsuro Sano, Naoto Ishibashi, Manabu Hashimoto, Masataka Okuno, Hisataka Moriwaki, Rikako Suzuki, Hiroyuki Kohno and Takuji Tanaka

in Carcinogenesis

Volume 25, issue 6, pages 979-985
Published in print June 2004 | ISSN: 0143-3334
Published online June 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh093
An acyclic retinoid, NIK-333, inhibits N-diethylnitrosamine-induced rat hepatocarcinogenesis through suppression of TGF-α expression and cell proliferation

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The present study was designed to determine the effects of NIK-333, a synthetic acyclic retinoid, on N-diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male F344 rats. Animals were given DEN dissolved in drinking water at a concentration of 40 p.p.m. for 5 weeks and then provided with drinking water free of DEN for 15 weeks to induce hepatocellular neoplasms. NIK-333 was administered orally (once a day) to rats at doses of 10, 40 and 80 mg/kg body wt for 14 weeks, starting 1 week after the completion of administration of DEN. At 20 weeks after the start of DEN administration, histopathological evaluation was carried out on all animals. The effects of NIK-333 on the cell proliferation activity of non-tumorous areas and liver tumor cells and the immunohistochemical expression of transforming growth factor-α (TGF-α) were also evaluated. NIK-333 at 40 and 80 mg/kg body wt significantly inhibited hepatocarcinogenesis (P < 0.05). In addition, NIK-333 at the same doses decreased DEN-induced overexpression of TGF-α in hepatocellular neoplasms (adenomas and carcinomas) and their surrounding tissue. Furthermore, NIK-333 significantly inhibited cell proliferation activity in the lesions and in non-tumorous areas (P < 0.01). Our results suggest that NIK-333 inhibits DEN-induced hepatocarcinogenesis through suppression of TGF-α expression and cell proliferation.

Keywords: AgNORs, argyrophilic nucleolar organizer regions; DEN, N-diethylnitrosamine; HBV, hepatitis virus B; HCC, hepatocellular carcinoma; HCV, hepatitis virus C; RA, retinoic acid; TGF-α, transforming growth factor-α

Journal Article.  5003 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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