Can people with loss-of-function mutations to CYP2E1 be resistant to benzene poisoning?

Can people with loss-of-function mutations to CYP2E1 be resistant to benzene poisoning?

• (also what about ethanol poisoning too?)

• Answer:

  Yes, it does. Benzene metabolism (in relation to its poisoning) is ascribed to two enzymes; cytochrome p450 2E1 (CYP2E1) and quinone oxidoreductase. While a decrease in the concentration or activity of the enzyme CYP2E1 may relieve the symptoms of benzene toxicity, but the latter enzyme is a requisite in counteracting the toxicity. Benzene is metabolised by CYP2E1 to benzene oxide (supposedly) which is known to be carcinogenic and bring about cytotoxic and genotoxic effects which results in the frank manifestation of the symptoms of toxicity. Thus repression in expression of this enzyme or mutations involving the reading frame of this enzyme both of which is grossly evident as a decrease in function or activity of this enzyme results in less production of the active metabolite and thus doesnt express the symptoms of poisoning which is evident as resistance being developed to benzene poisoning. And relating to ethanol, I am not sure of such an effect, in fact, chronic alcoholism induces this isoenzyme (CYP2E1). The ingested alcohol is metabolized by CYP2E1 ( others are alcohol dehydrogenase and catalase) and thus relieves the body of alcohol toxicity. And thus, if there's any mutational deficiency of CYP2E1 it will lead rather to a toxicity by itself due to decreased alcohol metabolism (though light or binge drinking is looked after by alcohol dehydrogenase)