Chemical carcinogens are usually chemically inert and require metabolic activation by cellular enzymes to exert their detrimental effects. A particular compound can be activated into an electrophile capable of covalently binding to cellular macromolecules. High concentrations of the reactive species can cause cell toxicity and death. Sublethal doses can result in cell transformation resulting from mutations in genes encoding enzymes or factors controlling cell division such as oncogenes or tumor suppressor genes. Another route of metabolism of a potentially harmful chemical is by detoxification or inactivation. Electrophilic metabolites can be rapidly neutralized by conjugating enzymes such as glutathione transferases. A procarcinogen can also be metabolized in ways that do not produce an active metabolite but a metabolite that is processed for elimination. It is generally believed that metabolism of chemical carcinogens plays a major role in the etiology of most human cancers. Thus, understanding the nature of carcinogen-metabolizing enzymes will aid in studies of human risk assessment. In particular, it will be possible to predict with more certainty the potential for cancer induction in humans by chemicals under development as foods additives, pesticides, or herbicides. Precise characterization of human enzymes that metabolize foreign compounds will also facilitate studies determining individual risk from carcinogen exposure. Foreign compound metabolizing enzymes have historically been grouped into those carrying out phase I and phase I1 reactions [I]. The former carry out hydrolytic and oxidation reactions and the latter, conjugation reactions. Although phase I enzymes are generally responsible for carcinogen activation, with certain chemicals such as arylamines and vinyl halides, conjugating enzymes participate in their metabolic activation. One of the earliest and most remarkable findings was that there exist tremendous species differences in animal handling of foreign chemicals [21. Almost all of the known foreign compound metabolizing enzymes also exhibit polymorphisms in their activities and expression [3]. Species differences and polymorphisms reaffirm the necessity to study human phase I and phase 11 enzymes in great detail.