Cytochrome P-450 Dependent Hydroxylation of Chemical Carcinogens

Hong, Y S

Abstract

A large number of chemicals have the ability to induce cancer in a variety of tissues of various hosts, including man. Despite current interest in the viral etiology of a limited number of specific human cancers, it is generally believed that most human cancers may be caused by chemicals present either as environmental contaminants or produced in certain instances from endogenous factors. Although great advances have been made in studies of the metabolism of many chemical carcinogens and on mechanisms of their reaction with cellular constituents the fact stands out that we do not understand the pathobiological action of single chemical carcinogen. It has been known for along time that many classes of chemical carcinogens become covalantly bound to DNA. RNA, and proteins of the cells in target tissues. It has become axiomatic that the induction of cancer by chemical carcinogens results from such covalent binding to one or more of these cellular macromolecules. However, despite much intensive reserch, the macromolecular target has not yet unequivocally been identified. Among the important classes of chemical carcinogens that become covalently bound to tissue macromolecules are polycyclic aromatic hydrocarbons(PAH), aromatic amines, nitrosamines, and aflatoxins. These carcinogens must be matabolized to a chemically reactive form which then reacts to form covalent macromolecular complexes. The millers and others have discovered that these metabolic actvations are carried out primarily by the microsomal mixed function oxidases. These enzyme systems, which are usually considered detoxifying and drug metabolizing, are the same ones that activate chemicals to carcinogenic and mutagenic forms.

Cytochrome P-450 Dependent Hydroxylation of Chemical Carcinogens

Abstract

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