Occupational toluene exposure induces cytochrome P450 2E1 mRNA expression in peripheral lymphocytes.
Print workers are exposed to organic solvents, of which the systemic toxicant toluene is a main component. Toluene induces expression of cytochrome P450 2E1 (CYP2E1), an enzyme involved in its own metabolism and that of other protoxicants, including some procarcinogens. Therefore, we investigated the association between toluene exposure and the CYP2E1 response, as assessed by mRNA content in peripheral lymphocytes or the 6-hydroxychlorzoxazone (6OH-CHZ)/chlorzoxazone (CHZ) quotient (known as CHZ metabolic ratio) in plasma, and the role of genotype (5 -flanking region RsaI/PstI polymorphic sites) in 97 male print workers. The geometric mean (GM) of toluene concentration in the air was 52.80 ppm (10-760 ppm); 54% of the study participants were exposed to toluene concentrations that exceeded the maximum permissible exposure level (MPEL). The GM of urinary hippuric acid at the end of a work shift (0.041 g/g creatinine) was elevated relative to that before the shift (0.027 g/g creatinine; p < 0.05). The GM of the CHZ metabolic ratio was 0.33 (0-9.3), with 40% of the subjects having ratios below the GM. However, the average CYP2E1 mRNA level in peripheral lymphocytes was 1.07 (0.30-3.08), and CYP2E1 mRNA levels within subjects correlated with the toluene exposure ratio (environmental toluene concentration:urinary hippuric acid concentration) (p = 0.014). Genotype did not alter the association between the toluene exposure ratio and mRNA content. In summary, with further validation, CYP2E1 mRNA content in peripheral lymphocytes could be a sensitive and noninvasive biomarker for the continuous monitoring of toluene effects in exposed persons.
Sección de Toxicología, Centro de Investigación y de Estudios Avanzados, National Polytechnical Institute, CP 07360, Mexico City, Mexico.
Ania
A
Mendoza-Cantú
Fabiola
F
Castorena-Torres
Mario
M
Bermúdez de León
Bulmaro
B
Cisneros
Lizbeth
L
López-Carrillo
Aurora E
AE
Rojas-García
Alberto
A
Aguilar-Salinas
Maurizio
M
Manno
Arnulfo
A
Albores
D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000235:genetics*; D017931:DNA Primers; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005838:Genotype; D006626:Hippurates / Q000652:urine; D006801:Humans; D016273:Occupational Exposure; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014050:Toluene / Q000032:analysis / Q000633:toxicity*
D017931:DNA Primers; D006626:Hippurates; D012333:RNA, Messenger; D014050:Toluene; D019392:Cytochrome P-450 CYP2E1; C030514:hippuric acid