Abstract B62: Zinc supplementation reduces forestomach tumor burden in N-nitrosomethylbenzylamine-treated mice

Abstract

Abstract Zinc deficiency is associated with high incidences of esophageal and other human cancers. In addition, zinc status in plasma and white blood cells is a better indicator of tumor burden and stage of the disease in head and neck cancer patients than overall nutritional status. Research in rodents found that zinc insufficiency leads to a highly proliferative hyperplastic condition in the upper gastrointestinal tract. Zn replenishment reduces the incidence of lingual, esophageal, and forestomach tumors in Zn-deficient rats and mice. While previous animal studies focused on the effect of Zn deficiency on cancer prevention and development, in this study we investigated the effect of Zn supplementation on carcinogenesis in Zn-sufficient mice of wild type and three tumor suppressor-deficient mouse strains, Fhit−/−, Fhit−/−Nit1−/−, and Fhit−/−Rassf1a−/−. About fifty mice from each strain received 6-8 doses of N-nitrosomethylbenzylamine (NMBA). Half the mice then received Zn supplemented water while another half received regular water. Sixteen weeks after last NMBA administration, mice were sacrificed and tumors were found only in forestomach. Mice without Zn supplementation had developed more tumors than Zn-supplemented mice: wild type C57BL/6 mice developed an average of 7.0 vs 5.0 tumors for Zn supplemented (p<0.05); Zn-supplemented Fhit−/− mice averaged 5.7 vs 8.0 for control mice (p< 0.01); Zn-supplemented Fhit−/−Nit1−/− mice averaged 5.4 vs 9.2 for control mice (p< 0.01); and Zn-supplemented Fhit−/−Rassf1a−/−mice averaged 5.9 vs 9.1 for control mice (p< 0.01). Zn supplementation reduced tumor burdens by 28% (wild type) to 42% (Fhit−/−Nit1−/−). Histological analysis of forestomach tissues also showed significant decreases in severity of preneoplastic and neoplastic lesions in Zn-supplemented cohorts of each mouse strain. Thus, Zn supplementation significantly reduced tumor burdens in mice with multiple tumor suppressor deficiencies. When Zn supplementation was begun at 7 weeks after the final carcinogen dose, the reduction in tumor burden was the same as observed when supplementation began immediately after carcinogen dosing, suggesting that Zn supplementation may affect tumor progression rather than tumor initiation. Our study suggests that Zn could have an important role in tumor prevention and perhaps treatment of specific human cancers and should be more thoroughly studied in preclinical models. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B62.