Manipulating the in utero environment may alter the onset of cancers that appear later in the lives of mammals, according to a new University of Toronto study published in the journal Carcinogenesis.
“We know that cancer-causing agents can travel across the placenta and harm the developing embryo or fetus,” says Professor Peter Wells of the Leslie Dan Faculty of Pharmacy. “This study provides the first direct evidence that changing the uterus’s molecular environment — in this case, by increasing the presence of antioxidants by adding vitamin E to the mice’s diet — alters the carcinogenic process in adult life.”
Wells and doctoral student Connie Chen worked with pregnant mice that had been genetically altered to lack one or both copies of the p53 gene, which results in a high incidence of cancers among their offspring. Prior to and throughout pregnancy, these mice were given either a normal diet or one supplemented with a high dose of vitamin E. The offspring were then observed for DNA damage and the onset of cancer. Two additional control groups, with both copies of the p53 gene intact, were also used in the experiment, one of which was given the vitamin E supplemented diet.
“Increased levels of vitamin E reduced in utero deaths among the offspring from 40 per cent in the control groups to five per cent in the test groups. In contrast, surprisingly, it also increased the onset of cancer in the offspring,” Wells says. “Offspring that were exposed to vitamin E and lack one or both copies of the gene developed cancers nine per cent and 21 per cent faster than the equivalent control groups.”
The amount of DNA damage also varied according to the concentration of vitamin E in tissue areas. Skin tissue from vitamin E-exposed offspring showed increased DNA damage, suggesting a potential mechanism for cell-specific enhancement of cancer, while brain tissues showed a decrease and liver tissue was unaffected.
Wells says that the selective effect of high-dose vitamin E on tissues in this study may explain why the vitamin has had different effects on different cancers and populations in other studies, and reveals the importance of tissue types in cancer study design. In contrast to high-dose vitamin E, preliminary studies using a much lower dietary dose found a protective effect, suggesting that optimal adjustments to the in utero environment, which may increase a fetus’s protection from oxidative stress, could prolong the time before some cancers occur and reduce the rate at which they spread.
The Canadian Institutes of Health Research and the (American) National Institutes of Health funded this study.
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