The mechanisms underlying chemically mediated malignant transformation are to be explored. Model systems to be used include in vivo exposure of rodents to thioacetamide, ethionine, alkylnitrosamines, and amino azo dyes. In vitro exposure of hepatocyte cultures to these same agents will also be employed. Previous data show a modification of nuclear restriction of RNA species in liver cells exposed to carcinogens, potentially representing an initiating or a promoting event, or both. The major areas to be investigated include: (1) An analysis of the cell-free model of nuclear RNA transport to determine the role of high-energy bond hydrolysis as a driving force, and to assay for the significance of selection of RNA species both for secretion and for back-diffusion to the nucleus; (2) an analysis of in vivo restriction in the two-stage model of hepatocarcinogenesis to learn whether "nuclear leakage" is related to initiation or to promotion; and (3) a continuing effort to purify DNA-dependent RNA polymerase from rat liver, especially by separating the nicking enzyme from the polymerase in order to clearly assay for initiation. These experiments will be used to test the hypothesis that malignant transformation involves alterations in the transcription and processing of RNA, at least as a basis for the phenotypic expression in cancer.