In the treatment of several types of cancer, oncologists have used chemotherapy with success, particularly with regard to increasing the number of long-term survivors. A major disadvantage to chemotherapy, however, is that many of the agents used are also carcinogenic and may induce a second malignant neoplasm. This is of special concern for children undergoing chemotherapy since their potential life span places them at a greater risk of developing a second cancer induced by the agents. Since retinoids possess anticarcinogenic effects in a variety of experimental systems, we propose that studies be performed to determine if they will eliminate or reduce the carcinogenic potential of chemotherapeutic agents. Retinyl acetate was selected for evaluation on the basis of considerable data with experimental animals indicating its prevention of cancers of the mammary gland, skin, and lungs. Thirteen-cis-Retinoic acid was selected because of its effectiveness in preventing cancers of the urinary bladder and lungs. Three anticancer agents, procarbazine, 4(5)-(3, 3-dimethyl-1-triazeno)imidazole-5(4)-carboxamide (DTIC), and chlorambucil, were selected because they are widely used clinically, are highly carcinogenic in animals, and are thought to have different mechanisms of action. In the study of procarbazine-induced tumors in female Sprague-Dawley rats, retinyl acetate will be used because the induced cancers are expected to be found in the mammary gland. Thirteen -cis-Retinoic acid will be used in the studies of DTIC- and chlorambucil-induced tumors in female Swiss-Webster mice since the induced cancers are expected to be found primarily in the lungs. Since the chemotherapeutic agents also induce ovarian and uterine cancers, the effect of retinoids on these cancers will be evaluated. The data obtained in these studies will determine if retinoids can prevent the induction of cancers by anticancer agents and, more importantly, provide an experimental basis for the possible future use of retinoid supplements for patients undergoing chemotherapy.
