The objective of the proposed research is to continue a systematic investigation of enzymatic potentialities of the human placenta in terms of its capabilities for the biotransformation of drugs and other foreign chemicals. The principal focus will be upon the metabolism of chemicals and drugs known or suspected to be active as transplacental procarcinogens and promutagens. Emphasis will be placed upon the study of biochemical reactions involved in the conversion of chemical procarcinogens to proximate or ultimate carcinogenic and/or mutagenic species via bioactivation. Monoxygenases, frequently involved in xenobiotic bioactivation reactions, as well as in highly important steroidal hydroxylations, will be examined in detail, particularly with respect to the interactions of steroidal and procarcinogenic substrates. Bioactivation via nonoxidative reaction mechanisms also will be investigated. The relative rates of activating vs. inactivating reactions now seem to be extremely important determinants of the potential of environmental chemicals to produce carcinogenic or other pharmacologic and toxicologic effects in various tissues. Thus, rates of reactions leading to the inactivation of drugs and chemicals also will be studied in detail. The importance of such studies is indicated by the probable relationships of placental drug metabolic processes to: abnormal or unusual effects of drugs and chemicals on the pregnant mother, fetus and newborn (including transplacental carcinogenesis, teratogenesis, mutagenesis and fetotoxicity) and acute or chronic effects which might result in abnormalities of a biochemical, physiological or behavioral nature. The long-term research objective is to provide a better understanding of the basic mechanisms of placental function such that a more rational approach to drug therapy and the design of new drugs for use in the pregnant woman, unborn fetus and newborn child might be developed.