Vitamin A and its structural congeners (retinoids) have come under intense investigation within the last few years as chemopreventive and, to a lesser extent, chemotherapeutic agents for cancer. Addition of carrots to rodent diets or administration of naturally-occurring retinoids have been reported to provide varying degrees of prophylaxis against chemically-induced neoplasia. A number of retinoids have entered phase I and II clinical trials. The hypervitaminosis A intoxication syndrome in humans and animals accompanies the use of prolonged administration of the vitamin, a protocol necessary for the successful prevention of cancer. Molecular modification of the ring, the polyene side chain and/or the polar terminus of the vitamin allow for changes in tissue distribution., intrinsic activity and toxicity. Administration of retinoids in patients has been linked to the production of human malformations following maternal treatment during the first trimester of pregnancy. The malformation syndrome in rodents is similar to that observed in human infants. The purpose of the present study is to assess the structure-activity relationships of retinoids in abnormal embryonic development and to provide data on the relative hazard associated with administration of retinoids. To provide an understanding of the pathological effects of rodents on mammalian embryonic development, administration of retinoids followed by histopathological inspection of early embryos will provide data on the morphogenesis of the malformations. Studies on the placental permeability and tissue distribution of the retinoids will be related to the teratogenic potential of the retinoids. The information obtained will be useful in clinical risk assessment of retinoid therapy in oncology and dermatology and will be of value in future design of retinoids which have the desirable chemopreventive properties, but which lack the undesirable teratogenic activity.
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