title: 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.affiliation: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Canada.
authors.forename: Arsalan S
authors.initials: AS
authors.lastname: Haqqani
authors.forename: Jagdeep K
authors.initials: JK
authors.lastname: Sandhu
authors.forename: H Chaim
authors.initials: HC
authors.lastname: Birnboim
mesh_terms: D000818:Animals; D004032:Diet; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics* / Q000276:immunology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009504:Neutrophils / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D019076:Transgenes; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D016209:Interleukin-8; D014810:Vitamin E; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D007041:Hypoxanthine Phosphoribosyltransferase