Dietary vitamin E affects neutrophil distribution and genetic instability in murine Mutatect tumors.

Abstract

Vitamin E is best known for its ability to scavenge reactive oxygen and nitrogen species. Solid tumors are frequently infiltrated with leukocytes, a potential source of these reactive species. The Mutatect tumor model is a fibrosarcoma that can be grown subcutaneously in syngeneic C57BL/6 mice. We previously showed that these tumors are infiltrated with neutrophils and that the number of neutrophils correlates with the number of hypoxanthine phosphoribosyl transferase (hprt) mutations and loss of an interleukin-8 (IL-8) transgene. Neutrophils are a source of nitric oxide, and tumors contain nitrotyrosine, a marker of damage by nitric oxide-related species. We also showed previously that dietary vitamin E supplements markedly lower the frequency of hprt mutants and the level of myeloperoxidase (a neutrophil marker) in a tumor fraction containing "loosely bound" cells. In the present report, we examine the effect of dietary vitamin E in greater detail. No effect on inducible nitric oxide synthase expression or nitrotyrosine levels was observed. However, dietary vitamin E induced a major redistribution of neutrophils from the loosely bound cellular fraction to the "stromal" fraction, while the total number of neutrophils in tumors was essentially unchanged. The loss of the IL-8 transgene seen earlier in Mutatect tumors was largely prevented. Vitamin E also prevented the large increase in hprt mutants (in the cellular and stromal fractions). Thus vitamin E appears to be protective against genotoxicity by scavenging reactive species, but also its ability to affect the distribution of neutrophils within tumors may be important.

• Authors: Arsalan S Haqqani, Jagdeep K Sandhu, H Chaim Birnboim
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 42 Issue 1 Pg. 105-11 ( 2002) ISSN: 0163-5581 [Print] United States
• PMID: 12235641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-8
• Vitamin E
• 3-nitrotyrosine
• Tyrosine
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Hypoxanthine Phosphoribosyltransferase

Topics

• Animals
• Diet
• Female
• Fibrosarcoma (genetics, immunology)
• Hypoxanthine Phosphoribosyltransferase (genetics)
• Interleukin-8 (genetics)
• Mice
• Mice, Inbred C57BL
• Mutation
• Neutrophils (physiology)
• Nitric Oxide Synthase (genetics)
• Nitric Oxide Synthase Type II
• Transgenes
• Tyrosine (analogs & derivatives, analysis)
• Vitamin E (administration & dosage)