Carcinogens, Drugs, and Cytochromes P-450

Abstract

A preponderance of xenobiotics, including chemical carcinogens and drugs as well as such physiologic compounds as steroids and prostaglandins, are metabolized by the mixed-function oxidases that contain cytochromes P-450.^{1 2 3 4} In 1973 Kellermann and colleagues reported that the inducibility of the cytochrome P-450 enzyme aryl hydrocarbon hydroxylase (AHH) in lymphocytes showed a trimodal distribution in human beings⁵ and that high inducibility was associated with an increased occurrence of bronchogenic carcinoma.⁶ These reports suggested a genetic basis for cancer susceptibility and attracted international attention, but they were subsequently disputed by Paigen et al.,⁷ who studied a large series of patients with lung . . .