This proposal is to study the mechanism(s) of malignant transformation in cell culture using various DNA inhibitors and other agents. The majority of these drugs are also chemotherapeutic agents now being used or proposed for use in man. Thus, the relative potential for these agents to produce secondary malignancies should be determined. The cell cycle specificity of malignant transformation will be also studied as well as specific chromosomal changes produced. Finally, mutagenic activity, effect on DNA repair; semiconservative DNA synthesis; C-type RNA virus activation and fibrinolysin and DNA strand break production following treatment with these agents will be investigated.