Abstract B64: Zinc supplementation has antitumor effects in 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis

Abstract

Abstract Zinc (Zn)-deficiency promotes esophageal/tongue tumorigenesis in rats by causing cell proliferation and changes in gene expression and Zn-replenishment inhibits tumorigenesis by attenuating cell proliferation and abnormal gene expression. Whether Zn has antitumor activities in a Zn-sufficient animal, however, is unknown. Here we examined the effects of Zn supplementation on tongue carcinogenesis in Zn-sufficient male Sprague-Dawley rats formerly exposed for 8 weeks to the carcinogen 4-nitroquinoline 1-oxide (NQO) at 10 and 20-30 ppm dose levels. Immediately after the cessation of NQO exposure, Zn gluconate (0, 20 ppm) was administered in the drinking water and continued for 10-13 weeks. At both NQO levels, Zn-supplemented rats had fewer tongue lesions than respective controls (10 ppm NQO: 5.2 ± 0.4 vs 8.6 ± 0.7, P<0.001; 20-30 ppm NQO: 10.6 ± 1.1 vs. 18.4 ± 1.2, P<0.01). Additionally, Zn-supplementation reduced the incidence of early tongue squamous cell carcinomas (SCC) from 40% [10/25] to 11.5% [3/26] (P=0.027) and that of invasive SCC from 93.8% [15/16] to 47.1% [8/17] (P=0.007) in rats exposed to 10 and 20-30 ppm NQO, respectively. The cell proliferative activity, as measured by quantitative proliferating cell nuclear antigen (PCNA)-immunohistochemistry, was significantly lower in the nontumorous tongue epithelia from Zn-supplemented rats than untreated controls (P<0.001). Compared with invasive tongue SCC from controls, Zn treatment led to less proliferative tongue SCCs with reduced immunostaining of cyclin D1, COX-2, NF-kB p65, and p53 proteins but increased apoptotic index. Thus, our finding that Zn inhibits tongue cancer progression in Zn-sufficient as in Zn-deficient animals should lead to prevention and therapeutic possibilities for oral cancer. Supported by National Institute of Health Grants R01CA118560 (LYYF) and R01 CA115965 (CMC). Citation Information: Cancer Prev Res 2010;3(12 Suppl):B64.