Risk assessment: toxicity from chemical exposure resulting from enhanced expression of CYP2E1.

Humans are continuously exposed to a wide variety of xenobiotics either voluntarily or from environmental exposure. Many xenobiotics including pesticides, nitrosamines, polycyclic aromatic hydrocarbons and halogenated hydrocarbons, require bioactivation by P450 enzymes to elicit toxicity. CYP2E1 is considered to be toxicologically important in humans because of its capacity to produce intermediates that promote cytotoxicity and/or carcinogenicity from a number of xenobiotics. Importantly, CYP2E1 is present constitutively and its content can be modulated by a variety of factors including xenobiotics such as alcohol. Because hepatic concentrations of CYP2E1 can vary considerably from one individual to another, the extent of formation of toxic products also varies. Indeed, as hepatic concentrations increase so does the risk of toxicity from chemicals activated by this P450 enzyme. Many chemicals modulate CYP2E1 expression and exposure to one compound may alter the toxicological impact of another. Considering that CYP2E1 content is related to toxicity from chemicals, identifying subjects with elevated levels may lead to minimizing exposure in high risk individuals.