Role of biotransformation in conceptal toxicity of drugs and other chemicals

Many developmental toxicants and teratogens require prior metabolism to rea ctive species or free radicals to exert toxicity. Thus the knowledge of con ceptal biotransformation is absolutely critical in understanding toxicity o f these chemicals. Due to extremely low content of cytochrome P450 in the e mbryo and other conceptal tissues, the research focus in recent years has s teadily shifted toward enzymes capable of peroxidative oxidation of xenobio tics. At least three enzymes viz. lipoxygenase, peroxidase and prostaglandi n synthase, each capable of peroxidative xenobiotic metabolism, occur in co nceptal tissues of man and laboratory animals in biologically significant a mounts. This review mainly summarizes the available information on the enzy matic bioactivation of teratogens and developmental toxicants belonging to diverse classes such as drugs, pesticides, environmental contaminants, indu strial and other chemicals. Additionally, some discussion is devoted toward issues such as drug-drug interactions. The emerging new information on the peroxidative glutathione conjugate formation from xenobiotics is also pres ented. A critical need for gathering more information on this subject using different enzyme preparations from human conceptal tissues is stressed to avoid tragedies in the future.