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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #217763
Title: Vitamin C supplementation does not protect L-gulono-gamma-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy

Author
item LEE, CHUNG-WEI - MASS INST. OF TECH
item Wang, Xiang-Dong
item CHIEN, KUO-LIONG - HARVARD UNIV PUB HEALTH
item GE, ZHONGMING - MASS INST. OF TECH
item RICKMAN, BARRY - MASS INST. OF TECH
item ROGERS, ARLIN - MASS INST. OF TECH
item VARRO, ANDREA - UNIV OF LIVERPOOL, UK
item WHARY, MARK - MASS INST. OF TECH
item WANG, TIMOTHY - COLUMBIA UNIVERSITY, NY
item FOX, JAMES - MASS INST. OF TECH

Submitted to: International Journal of Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2007
Publication Date: 3/1/2008
Citation: Lee, C., Wang, X., Chien, K., Ge, Z., Rickman, B.H., Rogers, A.B., Varro, A., Whary, M.T., Wang, T.C., Fox, J.G. 2008. Vitamin C supplementation does not protect L-gulono-gamma-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy. International Journal of Cancer. 22(5):1068-1076.

Interpretive Summary: In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C-deficient mice, we that although supplementation with a high level of vitamin C achieved physiologically normal vitamin C levels in plasma and gastric tissue, this dose of vitamin C did not protect H. pylori-induced premalignant gastric lesions in mice. In addition, less severe gastric lesions in H. pylori infected supplemented with low vitamin C correlated with an attenuated inflammatory response.

Technical Abstract: In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C-deficient B6.129P2-Gulo tm1Umc/mmcd (gulo -/-) mice lacking L-gulono-gamma-lactone oxidase, we compared gastric lesions and Th1 immune responses in H. pylori-infected gulo -/- mice supplemented with low (33 mg/L) or high (3300 mg/L) vitamin C in drinking water for 16 or 32 weeks. Vitamin C levels in plasma and gastric tissue correlated with the vitamin C supplementation levels in gulo -/- mice. H. pylori infection resulted in comparable gastritis and premalignant lesions in wildtype C57BL/6 and gulo -/- mice supplemented with high vitamin C, but lesions were less severe in gulo -/- mice supplemented with low vitamin C at 32 weeks post infection. The reduced gastric lesions in infected gulo -/- mice supplemented with low vitamin C correlated with reduced Th1-associated IgG2c, gastric IFN-gamma and TNF-alpha mRNA and higher H. pylori colonization levels. These results in the H. pylori-infected gulo -/- mouse model suggest that although supplementation with a high level of vitamin C achieved physiologically normal vitamin C levels in plasma and gastric tissue, this dose of vitamin C did not protect gulo -/- mice from H. pylori-induced premalignant gastric lesions. In addition, less severe gastric lesions in H. pylori infected gulo -/- mice supplemented with low vitamin C correlated with an attenuated Th1 inflammatory response.