Perinatal exposures may lead to increased risk of childhood cancers, as well as those later in life. Preconceptional parental, transplacental, and/or neonatal exposures may be involved. Studies with animal models are utilized to increase understanding of underlying cellular and molecular mechanisms. Among the exposures of concern is environmental tobacco smoke. Cigarette smoking by fathers has been implicated in increased risk of childhood cancers in at least six epidemiological studies. We investigated transplacental oxidative DNA damage, in the form of the promutagenic DNA adduct 8-oxo-dG, in fetuses of pregnant rats exposed to environmental tobacco smoke at a concentration within the range experienced by humans. There was organ- and gestation-stage specific increase in these adducts: kidneys were affected when exposure was stopped at gestation day 16 (mid-third trimester), whereas there were increases in fetal liver and brain 8-oxo-dG when exposure continued until the end of gestation. Pregnant mothers also showed damage in liver and kidney on day 16. The increases in 8-oxo-dG were highly significant and were of the same magnitude as increases in childhood cancer risk related to paternal smoking. Another possible mechanism of paternal effects on childhood cancer is male-mediated transgenerational carcinogenesis. We have found that treatment of male mice with a carcinogen before mating leads to changes in serum corticosterone, insulin-like growth factor 1, and glucose in their offspring, assessed at ten weeks after birth. Microarray analysis of gene expression in livers and lungs of these offspring confirm that the hormone and glucose changes are associated with tissue effects that could be related to development of neoplasms. AIDS Title:
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