The environment is filled with compounds known to be either toxic or carcinogenic. It is therefore important to understand how organisms respond to these agents at the cellular and molecular level. It is known that induction of cytochrome P-450 and other cellular proteins is a major part in the response. These proteins are involved in the ultimate metabolism of the xenobiotic agent but paradoxically, often activate its toxic and carcinogenic potential. The goal of this proposal is to define the regulation of a set of genes which are induced by aryl hydrocarbons in mice. We plan to apply previously used recombinant DNA technologies to identify the level of regulation of several cytochrome P-450 proteins and to extend the analysis to include other hydrocarbon inducible genes. The precise localization and characterization of the regulatory elements associated with these inducible genes will then be possible using gene transfer of the identified genes into appropriate cell types. By comparing a set of similarly regulated genes, the mechanisms of hydrocarbon gene regulation may be determined.