Molecular basis of individual susceptibility to xenobiotics

Living organisms are inevitably exposed to xenobiotics such as drugs, pollu tants or dietary compounds. These compounds are metabolized in order to ren der them more hydrophilic or less chemically reactive. The toxicity and pha rmacological activities of the resulting metabolites depend on the expressi on of xenobiotic metabolizing enzymes. The level of expression of these enz ymes is extremely variable, and is under the control of environmental, gene tic or patho-physiological factors. For example, (1) the variability of thi opurine methyl transferase explains the susceptibility to azathioprine and 6-mercaptopurine and (2) the variability in the metabolism of benzo(a)pyren e may be a risk factor in lung cancer among smokers. Therefore, differences in metabolism can explain, at least in part, individual susceptibilities t o xenobiotics.