The role of cytochrome P-450 in the toxicity of xenobiotics.

The cytochrome P-450 containing mixed-function oxidase system bound to the ergastoplasmic membrane plays an essential role both in the detoxification as well as in the activation of numerous xenobiotics. In many cases, this enzyme system initiates the formation of reactive electrophilic intermediates (epoxides, free radicals, carbenes) which may induce cytotoxic, mutagenic and carcinogenic effects by reacting with various cell constituents. In most cases, the active metabolites are covalently bound to the proteins and nucleic acids, but the binding to lipids or the initiation of the lipid peroxidation is also important. In the activation of xenobiotics by N-hydroxylation or N-dealkylation an aminoxidase is of special importance which is independent of cytochrome P-450. The intermediates arising from this enzyme reaction frequently become biologically active only after being stabilized by an ester bond.