The long-range purpose of this project is to study the mechanism of experimentally induced hepatomas and ovarian tumors. We are particularly interested in the role of environmental contaminants such as the polycyclic hydrocarbons, nitroso-compounds and N-acetylarylamines in initiating these tumors, as well as the role of genetic predisposition in development of these tumors. These tumors, at various time points during their development, will then be used as models for evaluating chemotherapeutic agents and other drugs which might be of therapeutic value. Topics of present interest are: (1) the role of metabolic activation, as well as the genetic control of activating enzymes, in the chemical initiation of hepatoma and ovarian tumors; (2) the time course of hepatoma and ovarian tumor initiation with particular emphasis on the changing enzyme patterns as the cells become increasingly dedifferentiated; (3) the role of nucleophilic agents such as N-acetylcysteine, L-cysteine and cysteamine in preventing the chemical initiation of tumors; (4) the characterization of cAMP and the Beta-receptor involvement in the chemical induction of hepatomas and the possible use of Beta-blockers and/or Beta-agonists in preventing the occurance of these hepatomas.