Cytochrome CYP2E1 phenotyping and genotyping in the evaluation of health risks from exposure to polluted environments.
Humans are exposed to over 70,000 man-made chemicals including drugs, food additives, herbicides, pesticides, and industrial agents. It is well established that environmental chemicals are the cause of numerous human diseases including cancer. In most cases, chemical carcinogens require metabolic activation, which is mainly achieved by P450s enzymes. CYP2E1 is of clinical relevance because it is inducible by ethanol, and it metabolizes many common organic solvents such as benzene, alcohols and halogenated solvents. Therefore, alteration in the level of CYP2E1 might influence the health effects of the environmental pollutants. This hypothesis needs to be validated by epidemiological studies and the objective of the "Biomed-2" project was to develop new tests to assess the individual metabolic capacity of workers exposed to volatile organic compounds in order to predict their occupational risk. In vivo chlorzoxazone 6-hydroxylation was validated as a non-invasive and selective test for the determination of liver CYP2E1 activity. Preliminary data in workers exposed to organic solvents indicated that chlorzoxazone metabolism may be a biomarker of occupational exposure to organic solvents. Other approaches, such as use of salicylate as catalytic probe or measurement of catalytic activity in lymphocytes, were not conclusive. Attempts to use CYP2E1 genotyping for estimating human risks from chemical exposure did not bring convincing data as genetic polymorphism of CYP2E1 could not be clearly related to its catalytic activity.
Lucas
D
D
Laboratoire de Biochimie, Faculté de Médecine de Brest, EA 948, BP 815, 29285 Brest Cedex, France. daniele.lucas@univ-brest.fr
Ferrara
R
R
Gonzales
E
E
Albores
A
A
Manno
M
M
Berthou
F
F
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002273:Carcinogens / Q000009:adverse effects* / Q000378:metabolism*; D002384:Catalysis; D002753:Chlorzoxazone / Q000737:chemistry; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D016021:Epidemiologic Studies; D005838:Genotype; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009125:Muscle Relaxants, Central / Q000737:chemistry; D016273:Occupational Exposure; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012459:Salicylates / Q000378:metabolism; D012997:Solvents / Q000009:adverse effects* / Q000378:metabolism*; D014835:Volatilization
D015415:Biomarkers; D002273:Carcinogens; D009125:Muscle Relaxants, Central; D012459:Salicylates; D012997:Solvents; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone