Journal of Korean Society of Occupational and Environmental Hygiene (한국산업보건학회지)

Korean Industrial Hygiene Association (한국산업보건학회)
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The effects of toluene on its metabolism and induction of cytochrome P-450(CYP)2B1/2 by xylene

Xylene에 의한 CYP2B1/2의 유도와 대사에 있어서 toluene의 영향

  • Kim, Ki-Woong (Occupational Safety and Health Research Institute, KOSHA) ;
  • Heo, Kyung-Hwa (Occupational Safety and Health Research Institute, KOSHA)
  • 김기웅 (한국산업안전보건공단 산업안전보건연구원) ;
  • 허경화 (한국산업안전보건공단 산업안전보건연구원)
  • Received : 2008.12.16
  • Accepted : 2009.03.17
  • Published : 2009.03.31
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Abstract

This study was undertaken to investigate the effects of single and combined exposure of toluene (T) and xylene (X) on the cytochrome-450(CYP)-mediated metabolizing capacity, induction of CYP isozymes and the excretion of their metabolites in urine. Animal were adults male Sprague-Dawley (SD) rats and divided into 4 groups such as control, T (treated with 63.7 mg/body kg), X (treated with 65.9 mg/body kg) and TX(T=X). Organic solvents was administrated by intraperitoneal injection for 3 days. The contents of protein and CYP in liver microsomes of control group were $16.48{\pm}0.56 mg/m{\ell}$ and $0.744{\pm}0.025$ nmol/mg protein, respectively, and they contents were significantly lower than in derived from treated groups (p<0.01). The activities of PROD and ${\rho}NPH$ were significantly higher in single treated groups than in control and combined group (TX). When Western immunoblotting were carried out with two monoclonal antibodies (MAb 1-98-1 and MAb 2-66-3) which were specific against CYP2B1/2 and CYP2E1, respectively, a strong signal corresponding to CYP2B1/2 was observed in microsomes obtained from rats treated with X and TX. The color density against CYP2E1 was slightly increased in T and TX groups compared with C and X groups. The amounts of urinary hippuric acid in T single treated group was $3.29{\pm}1.97$ g/g creatinine and TX combined group was $2.91{\pm}1.76$ g/g creatinine, but was not significant. However, amount of urinary methy hippuric acid in X single treated group ($1.62{\pm}0.72$ g/g creatinine) was significantly higher than TX combined group ($0.93{\pm} 0.63$ g/g creatinine)(p<0.01). These results suggested that CYP2E1 isozyme might be responsible for the metabolism of T, and CYP2B1/2 isozyme is for X. And also, difference of metabolites level between single and combined group may be speculated that the intermediates of T and X interacted each other in the process of their metabolite formation reaction.

Keywords

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