Journal Article

Zinc supplementation suppresses 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis

Louise Y.Y. Fong, Yubao Jiang, Maysoon L. Rawahneh, Karl J. Smalley, Carlo M. Croce, John L. Farber and Kay Huebner

in Carcinogenesis

Volume 32, issue 4, pages 554-560
Published in print April 2011 | ISSN: 0143-3334
Published online January 2011 | e-ISSN: 1460-2180 | DOI:
Zinc supplementation suppresses 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis

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Dietary zinc (Zn) deficiency is implicated in the pathogenesis of human oral–esophageal cancers. In rats, Zn deficiency causes increased cell proliferation and cyclooxygenase-2 (COX-2) overexpression and enhances oral carcinogenesis by 4-nitroquinoline 1-oxide (NQO). Zn replenishment reverses all these effects. We questioned whether Zn has antitumor efficacy in a Zn-sufficient animal by investigating in Zn-sufficient rats (i) the efficacy of Zn supplementation on the progression of tongue squamous cell carcinogenesis induced by drinking water exposure to high (20–30 p.p.m.) and low (10 p.p.m.) doses of NQO and (ii) the modulating effects of Zn supplementation on biomarker expression in tongue lesions by immunohistochemistry. In rats exposed to high doses of NQO, Zn supplementation significantly reduced the incidence of papillomas from 100 to 64.7% (P = 0.018) and invasive carcinomas from 93.8 to 52.9% (P = 0.017). In rats exposed to low doses of NQO, where only minimally invasive carcinomas developed, Zn supplementation significantly reduced tumor multiplicity, incidence of tumors (1–2 mm), hyperplasia, dysplasia, papillomas and progression to carcinoma. Immunohistochemical analysis of carcinomas showed that Zn supplementation caused a shift to a less proliferative/aggressive cancer phenotype by reducing cell proliferation, stimulating apoptosis and decreasing expression of the key tumor markers cyclin D1, p53 and COX-2. Additionally, Zn supplementation significantly reduced cell proliferation in non-lesional tongue squamous epithelia, thereby suppressing tumor development. Together, the results demonstrate that Zn supplementation has chemopreventive efficacy against oral carcinogenesis in nutritionally complete animals. Our data suggest that Zn supplementation may be efficacious in the chemoprevention of human oral cancer.

Journal Article.  5245 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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