1. In vivo CYP2E1 phenotyping as a new potential biomarker of occupational and experimental exposure to benzene
- Author
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Mariella Carrieri, M. Di Mare, P. Piccoli, M.E. Fracasso, Maurizio Manno, Gb Bartolucci, L. Padovano, José Salvador Lepera, P., Piccoli, M., Carrieri, L., Padovano, M., Di Mare, G. B., Bartolucci, M. E., Fracasso, J. S., Lepera, and Manno, Maurizio
- Subjects
Male ,medicine.medical_specialty ,Stereochemistry ,Metabolite ,Benzene ,CYP2E1 ,Chloroxazone ,6-OH-chloroxazone ,Metabolic phenotype ,Toxicology ,Statistics, Nonparametric ,Rats, Sprague-Dawley ,Random Allocation ,chemistry.chemical_compound ,In vivo ,Occupational Exposure ,Internal medicine ,PEG ratio ,medicine ,Animals ,Humans ,Chromatography, High Pressure Liquid ,Area under the curve ,Cytochrome P-450 CYP2E1 ,General Medicine ,Sorbic Acid ,Acetylcysteine ,Rats ,chlorzoxazone ,Phenotype ,Endocrinology ,chemistry ,Area Under Curve ,Chlorzoxazone ,Toxicity ,Biomarkers ,Corn oil ,medicine.drug - Abstract
Assessing CYP2E1 phenotype in vivo may be important to predict individual susceptibility to those chemicals, including benzene, which are metabolically activated by this isoenzyme. Chlorzoxazone (CHZ), a specific CYP2E1 substrate, is readily hydroxylated to 6-OH-chlorzoxazone (6-OH-CHZ) by liver CYP2E1 and the metabolic ratio 6-OH-CHZ/CHZ in serum (MR) is a specific and sensitive biomarker of CYP2E1 activity in vivo in humans. We used this MR as a potential biomarker of effect in benzene-treated rats and, also, in humans occupationally exposed to low levels of benzene. Male Sprague-Dawley rats (375-400g b.w.) were treated i.p. for 3 days with either a 0.5ml solution of benzene (5mmol/kg b.w.) in corn oil, or 0.5ml corn oil alone. Twenty-four hours after the last injection, a polyethylene glycol (PEG) solution of CHZ (20mg/kg b.w.) was injected i.p. in both treated and control animals. After 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, and 240min from injection, 0.2ml blood was taken from the tip tail and stored at -20 degrees C until analysis. A modified reverse phase HPLC method using a 5microm Ultrasphere C18 column equipped with a direct-connection ODS guard column, was used to measure CHZ and its metabolite 6-OH-CHZ in serum. No statistically significant difference in the MR was observed, at any sampling time, between benzene-treated and control rats. The concentration-versus-time area under the curve (AUC), however, was lower (p
- Published
- 2010