Our objective is to investigate the influence of DNA modification on pregnancy. The immediate goal is to investigate how DNa damage is altered during pregnancy and fetal development and how the mother and fetus can repair such damage. The effects of gestation age and chemical class on these two parameters will be studied in mice. The susceptibility of mice to chemical toxicity during pregnancy and fetal development will be investigated. Species differences in DNA adduction will be carried out in animals such as mouse, hamster, guinea pig, and rabbit, which have different placental morphologies and rates of intrauterine development, to enable a better interpretation to the hazards of exposure in humans. A 32P-postlabeling method was recently developed in our laboratory, which allows the detection of one covalently bound chemical molecule per genome, does not require the administration of radioactive carcinogen to animals, and can detect DNA modification in milligram quantities of tissues. This method is ideally suited for investigating DNA damage during pregnancy and fetal development. Additionally, the effects of DNA adduction on DNA methylation in rapidly proliferating fetal tissues will be investigated. Results obtained will help in elucidating if there are periods of increased susceptibility to chemical toxicity during gestation and in improving human prenatal care in order to ensure healthy pregnancy, offspring, and mothers.
