| First Author | Chen CS | Year | 2009 |
| Journal | Cancer | Volume | 115 |
| Issue | 7 | Pages | 1563-75 |
| PubMed ID | 19195043 | Mgi Jnum | J:151126 |
| Mgi Id | MGI:4352808 | Doi | 10.1002/cncr.24130 |
| Citation | Chen CS, et al. (2009) Reduced tumorigenesis in p53 knockout mice exposed in utero to low-dose vitamin E. Cancer 115(7):1563-75 |
| abstractText | BACKGROUND: The limited antioxidative capacity of the fetus renders it more susceptible to reactive oxygen species (ROS), and possibly to ROS-mediated cancer initiation or promotion in utero. METHODS: To test this hypothesis, pregnant cancer-prone p53 knockout mice were prenatally supplemented with a low dietary dose of the antioxidant vitamin E (VE) (0.1% all-rac-alpha-tocopherol-acetate), and the homozygous (-/-) and heterozygous (+/-) p53-deficient and wild-type (+/+) offspring were examined for VE levels, oxidative DNA damage, chromosomal stability, cellular viability and postnatal tumorigenesis. RESULTS: In utero exposure to VE reduced spontaneous postnatal tumorigenesis in p53 +/- offspring, and increased VE levels and reduced fetal DNA oxidation in some but not all tissues of p53-deficient fetuses. Survival of VE-exposed p53 +/- offspring at the end of the study was double that of the +/- controls (45% vs 23%). In primary culture of skin fibroblasts from VE-exposed fetuses, VE did not alter chromosomal ploidy, but reduced cell death, indicating that its protective effect did not involve chromosomal stability. CONCLUSIONS: The tissue-selective increase in fetal VE levels and reduced DNA oxidation, together with a concomitant reduction in postnatal tumorigenesis, suggest that in utero oxidative stress contributes to some postnatal cancers, and the risk can be reduced by maternal dietary supplementation with low-dose VE. |
