title: Vitamin C supplementation does not protect L-gulono-gamma-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy.
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 (3,300 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.
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Chung-Wei
authors.initials: CW
authors.lastname: Lee
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Wang
authors.forename: Kuo-Liong
authors.initials: KL
authors.lastname: Chien
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Ge
authors.forename: Barry H
authors.initials: BH
authors.lastname: Rickman
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Rogers
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
authors.forename: Mark T
authors.initials: MT
authors.lastname: Whary
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D005260:Female; D005756:Gastritis / Q000382:microbiology / Q000517:prevention & control*; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D050544:L-Gulonolactone Oxidase / Q000172:deficiency*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D017452:Receptors, IgG / Q000276:immunology; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C406563:IgG2c receptor; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid