Occupational Toluene Exposure Induces Cytochrome P450 2E1 mRNA Expression in Peripheral Lymphocytes Ania Mendoza-Cantú,1 Fabiola Castorena-Torres,1 Mario
Bermúdez de León,2 Bulmaro Cisneros,2 Lizbeth
López-Carrillo,3 Aurora E. Rojas-García,1 Alberto
Aguilar-Salinas,4 Maurizio Manno,5 and Arnulfo Albores1 1Sección de Toxicología and 2Departamento
de Genética y Biología Molecular, Centro de Investigación
y de Estudios Avanzados, National Polytechnical Institute, Mexico City, Mexico; 3Centro
de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública,
Cuernavaca, Morelos, Mexico; 4Coordinación Nacional de Salud
en el Trabajo, Centro Médico Nacional Siglo XXI, Instituto Mexicano
del Seguro Social, Mexico City, Mexico; 5Dipartimento di Scienze
Mediche Preventive, Sezione di Tossicologia Occupazionale, Università degli
Studi di Napoli “Federico II,” Naples, Italy Abstract 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. Key words: chlorzoxazone, CYP2E1 mRNA induction, lymphocytes, occupational exposure, toluene. Environ Health Perspect 114:494-499 (2006) . doi:10.1289/ehp.8192 available via http://dx.doi.org/ [Online 13 October 2005]
Address correspondence to A. Albores, Sección de Toxicología, Cinvestav-IPN, Ave. IPN 2508, Col. Zacatenco, CP 07360, Mexico City, Mexico. Telephone: 52-55-5061-3308. Fax: 52-55-5061-3395. E-mail: aalbores@cinvestav.mx We thank L.M. Del Razo and L. Sarkissian for critical review and R.A. Reyes Mejía and M.L. López González for analytical work. This investigation was supported by CONACYT Mexico (project M0061-M9602) , which also provided a grant to A.M.-C. (95754) , and the Mexico-Italy Cooperation Program 2003-2005 (project 27) . The authors declare they have no competing financial interests. Received 11 April 2005 ; accepted 12 October 2005. The full version of this article is available for free in HTML or PDF formats. |