Abstract
Helicobacter pylori infection is a known risk factor for gastric cancer. We hypothesized that H. pylori infection would lead to the sustained production of the reactive nitrogen species nitric oxide and peroxynitrite as part of the host immune response. We further hypothesized that H. pylori infection would lead to increased apoptosis of gastric epithelial cells, possibly in response to free radical-mediated DNA damage. Using immunohistochemistry, we stained and scored gastric antral biopsies from 84 Colombian patients with nonatrophic gastritis before and after treatment for H. pylori infection. We examined expression of inducible nitric oxide synthase (iNOS); nitrotyrosine, a marker for peroxynitrite; and DNA fragmentation, a marker for apoptosis. Patients were treated with triple therapy (amoxicillin, 500 mg three times a day for 2 weeks; metronidazole, 400 mg three times a day for 2 weeks; and bismuth subsalicylate, 262 mg four times a day for 2 weeks, followed by 262 mg every day for 4–12 months). Eradication of H. pylori infection resulted in a significant reduction in iNOS and nitrotyrosine staining and a marginally significant reduction in apoptosis. Dietary supplementation with β-carotene (30 mg every day for 4–12 months) resulted in a significant decrease in iNOS staining. Supplementation with ascorbic acid (1 g twice a day for 4–12 months) led to a significant reduction in nitrotyrosine staining. In patients supplemented with either ascorbic acid or β-carotene, there was a trend toward a reduction in apoptosis, but this was not statistically significant. We conclude that H. pylori infection is accompanied by the formation of endogenous reactive nitrogen intermediates, which may contribute to DNA damage and apoptosis. In addition to antimicrobial therapy, dietary supplementation with β-carotene and ascorbic acid may prevent the formation of these potential carcinogens.
Footnotes
-
↵1 This study was funded in part by Program Project PO1-CA28842 of the National Cancer Institute, NIH, USPHS.
-
↵2 These authors contributed equally to this article.
-
↵3 To whom requests for reprints should be addressed, at Department of Pathology, Louisiana State University Medical Center, 1901 Perdido Street, New Orleans, LA 70112.
- Received February 7, 1996.
- Accepted May 10, 1996.
- ©1996 American Association for Cancer Research.
Volume 56, Issue 14
