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.