P450 enzymes have been implicated in the toxicity of organic chemicals, active through a variety of mechanisms. In particular, CYP1 and CYP2E enzymes are most closely associated with the metabolic activation of pro-carcinogens and other toxicants in animal models. The majority of definite human carcinogens are either direct-acting electrophiles or are metabolically activated by P450 enzymes, especially those of the CYP1 family. Electronic and molecular structural features of organic chemicals appear to pre-dipose them either to activation by one P450 or detoxification by an alternative enzyme. Moreover, the rate of P450-mediated metabolism can be linked quantitatively to frontier orbital parameters, whereas CYP1 induction potency appears to be determined by a combination of molecular shape and electron activation.
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