A patas monkey model was employed to investigate transplacental formation of DNA adducts in fetal tissues after exposure to cisplatin, a therapeutic drug sometimes administered to pregnant women, and, in a separate series of experiments to benzo[a]pyrene (BP), an environmental polycyclic aromatic hydrocarbon carcinogen. The cisplatin was found to have considerable fetotoxicity. A total dose of 12 mg/m2 was found to support fetal viability and multiple tissues were examined in fetal monkeys taken by cesarean section. Cisplatin-DNA adducts were analyzed by ELISA and by atomic absorbance spectroscopy. Maternal tissues sustained approximately twice as much DNA damage as fetal tissues. There were significant levels of adducts in placenta, and these were especially prominent in the brains of the fetuses. These studies demonstrate that cisplatin does cross the primate placenta, and imply that human fetuses may experience DNA damage with possible tumor initiating consequences. BP induced high levels of DNA adducts in all fetal organs, placentae, and maternal livers when given during the first, second, or third trimesters. Adduct levels in fetal tissues were comparable to those in maternal liver and higher than predicted by concentrations of activating enzymes, suggesting transplacental passage of activated intermediates formed by maternal liver. Individual fetal organ adduct levels correlated significantly with placental adduct levels, indicating that placenta, an available tissue for human biomarker studies, is a reliable indicator of genotoxic injury sustained by the fetus. The slopes of linear regression lines of correlation analyses varied among organs and gestational stages, indicating a fetal contribution as well as a maternal contribution. Adduct levels were dose responsive in the fetal tissues, but with a lesser slope compared to placenta and maternal liver, suggesting significant interception of dose by the placenta. After cessation of treatment, adduct loss was biphasic, with 10% of these still detectable after 50 days.
