Studies carried over the last few decades have demonstrated that the fetus is susceptible to the carcinogenic action of many of todays chemicals commonly found in the work environment. In addition, recent evidence has suggested that this harmful effect can be passed along to future unexposed generations. The objective of this proposal is to establish the sensitivity of the fetus to chemical carcinogens and whether the effects of alcohol comsumption modifies this effect both in the immediate and future offspring. This project has thus been designed to test the hypothesis that in utero exposure to 1, 2-dimethylhydrazine (DMH) results in carcinogenic information that is incorporated in the somatic and germ cells of both the immediate and future progeny; and that alcohol consumption during pregnancy alters the sensitivity of the fetus to the effects of this chemical carcinogen. Testing of this hypothesis will be accomplished by determining the specific antitumor cell-mediated immunity (CMI) in Fisher F344 inbred rats, brought about by exposure to DMH and alcohol. Pregnant rats will be administered a 5% alcohol solution on day 6 of gestation followed by a subcutaneous injection of varying doses of DMH (0.0001 to 0.1 mg./kg.). Antitumor CMI measurements will be determined 60 days post-partum for the dams, F1, F2, and F3 generations. Sensitivity of the offspring to in utero exposure of DMH and alcohol will be delineated by calculations of an Alcohol Perinatal Sensitivity Factor (APSF) and a Fetal Workplace Risk Factor (FWRF). Work has already been completed on the effects of perinatal exposure to DMH in the first generation. These results have demonstrated a significant antitumor response in both sexes and a threshold level of 0.01 mg./kg., 10 times lower than adult exposure. Certainly, with the increasing numbers of women of child bearing age entering the industrial workforce, and the recent concern of alcohol consumption during pregnancy, it is of utmost importance that information be obtained on such health hazards. This proposal has been designed in an attempt to answer some of these questions by applying the bio-analytical techniques we have developed over the past years in our laboratory.