Journal Article

Modifying effects of dietary capsaicin and rotenone on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

Takuji Tanaka, Hiroyuki Kohno, Keiko Sakata, Yasuhiro Yamada, Yoshinobu Hirose, Shigeyuki Sugie and Hideki Mori

in Carcinogenesis

Volume 23, issue 8, pages 1361-1367
Published in print August 2002 | ISSN: 0143-3334
Published online August 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.8.1361
Modifying effects of dietary capsaicin and rotenone on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

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The effects of dietary administration of capsaicin and rotenone on 4-nitroquinoline 1-oxide (4-NQO)-induced tongue tumorigenesis were investigated in male F344 rats. In pilot studies, gavage with capsaicin and rotenone elevated the phase II enzymes glutathione S-transferase (GST) and quinone reductase (QR), in the liver and tongue. Also, a 10 week period of feeding of 500 p.p.m. capsaicin or rotenone together with 4-NQO exposure inhibited the occurrence of tongue dysplasia. Subsequently, a long-term study was conducted to test the protective effects of both compounds on 4-NQO-induced tongue carcinogenesis. One group was treated with 4-NQO alone (20 p.p.m. in drinking water for 8 weeks) and four other groups received the carcinogen treatment plus diets containing 500 p.p.m. test compounds for 10 weeks (initiation phase) or for 28 weeks (post-initiation phase). At the termination of the study (38 weeks), feeding of rotenone during the initiation phase, but not during the post-initiation phase, was found to significantly reduce the incidence of tongue squamous cell carcinoma (53% vs. 16%, 70% reduction, P b=e 0.0250) and severe dysplasia (80% vs. 42%, 70% reduction, P = 0.028). Capsaicin feeding during either the initiation or promotion phase and rotenone feeding during the promotion phase also reduced the frequency of tongue carcinoma without statistical significance. The treatment with two compounds especially rotenone lowered cell proliferation activity in the tongue, elevated phase II enzymes’ activities of the liver and tongue, and increased the apoptotic index of tongue carcinoma. Although our results suggest that rotenone feeding during the initiation stage prevented 4-NQO-induced tongue carcinoma, chronic intravenous exposure of rotenone reproduces several features of human Parkinson’s disease in rats (Nat. Neurosci., 3, 1301–1306, 2000), suggesting that additional studies to confirm the safety of rotenone are warranted.

Keywords: AP-1, activator protein 1; CDNB, 1-chloro-2,4-dinitrobenzene; COX, cyclooxygenase; DCNB, 1,2-dichloro-4-nitrobenzene; DMBA, 7,12-dimethylbenz[a]anthracene; GST, glutathione S-transferase; NF-κB, nuclear factor-kappa B; 4-NQO, 4-nitroquinoline 1-oxide; ODC, ornithine decarboxylase; PCNA, proliferating cell nuclear antigen; QR, quinone reductase; ssDNA, single stranded DNA

Journal Article.  6538 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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