This research examines mechanisms of frameshift mutagenesis by rat liver microsome-activated chemical carcinogens in terms of target DNA sequence. Various parameters will be followed to measure rat liver induction by specific chlorinated hydrocarbons. Differentially induced liver microsomes will be tested for potentiation of reverse and forward mutagenesis by carcinogens. New frameshift mutants will be characterized working from amino acid replacements using histidinol dehydrogenase of Salmonella typhimurium. Comparative studies of amino acid sequence will be made on the enzyme from S. typhimurium and Escherichia coli.