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Chemical carcinogenicity and the antineoplastic agents.

The subject of chemical carcinogenicity is reviewed with discussions of the involved environmental factors, proposed mechanisms of mutagenesis and carcinogenesis, dose-response considerations, secondary tumor development, and an emphasis on the potential carcinogenicity of antineoplastic agents. Although the causes of various cancers are complex, 70-90% of human cancers are thought to be caused by environmental factors. The factors that have been strongly implicated are excessive cigarette use, heavy alcohol consumption, and disordered dietary practices. Of the minor possible causes of cancer, the administration of prescribed pharmaceutical agents such as the antineoplastic drugs accounts for a suspected 1% of total cancer deaths in the United States. Chemical carcinogenesis involves a multistep process of initiation, promotion, and progression. The development of cancer in man usually takes several years and may be associated with specific tissue susceptibility. Although antineoplastic agents have been recognized for their potential ability to cause cancer, it is difficult to assess from the literature their actual carcinogenic effects in man. Important determinants that modify the ability of the host to deal with carcinogenic substances and the subsequent effects have not been fully evaluated. The control of chemical carcinogenesis must involve reduction of exposure to potential hazards wherever possible. To reduce the risks involved in handling antineoplastic agents, health-care professionals should follow a method of systematic avoidance by adhering to appropriate procedures.