Effect of zinc supplementation on N-nitrosomethylbenzylamine-induced forestomach tumor development and progression in tumor suppressor-deficient mouse strains
Autor: | Xueliang Pan, James Liu, Teresa Druck, Louise Y.Y. Fong, Carlo M. Croce, Nicola Zanesi, Jin Sun, Kay Huebner, Donald Quimby, Gerd P. Pfeifer |
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Rok vydání: | 2010 |
Předmět: |
Male
Cancer Research medicine.medical_specialty Pathology Tumor suppressor gene Ratón Blotting Western Tumor initiation Biology medicine.disease_cause Dimethylnitrosamine Immunoenzyme Techniques Mice Aminohydrolases Stomach Neoplasms Internal medicine medicine Animals Carcinogen Mice Knockout Tumor Suppressor Proteins Stomach General Medicine medicine.disease Acid Anhydride Hydrolases Neoplasm Proteins Mice Inbred C57BL medicine.anatomical_structure Endocrinology Zinc Compounds Tumor progression Dietary Supplements Carcinogens Carcinoma Squamous Cell Disease Progression Zinc deficiency Carcinogenesis Cancer Prevention |
Zdroj: | Carcinogenesis. 32:351-358 |
ISSN: | 1460-2180 0143-3334 |
DOI: | 10.1093/carcin/bgq251 |
Popis: | Zinc deficiency is associated with high incidences of esophageal and other cancers in humans and leads to a highly proliferative hyperplastic condition in the upper gastrointestinal tract in laboratory rodents. Zn replenishment reduces the incidence of lingual, esophageal and forestomach tumors in Zn-deficient rats and mice. While previous animal studies focused on Zn deficiency, we have investigated the effect of Zn supplementation on carcinogenesis in Zn-sufficient mice of wild-type and tumor suppressor-deficient mouse strains. All mice received N-nitrosomethylbenzylamine and half the mice of each strain then received Zn supplementation. At killing, mice without Zn supplementation had developed more tumors than Zn-supplemented mice: wild-type C57BL/6 mice developed an average of 7.0 versus 5.0 tumors for Zn supplemented (P < 0.05); Zn-supplemented Fhit−/− mice averaged 5.7 versus 8.0 for control mice (P < 0.01); Zn-supplemented Fhit−/−Nit1−/− mice averaged 5.4 versus 9.2 for control mice (P < 0.01) and Zn-supplemented Fhit−/−Rassf1a−/− (the murine gene) mice averaged 5.9 versus 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. |
Databáze: | OpenAIRE |
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