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KMID : 0895420090190010073
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Journal of Korean Society of Occupational and Enviromental Hygiene
2009 Volume.19 No. 1 p.73 ~ p.79
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The effects of toluene on its metabolism and induction of cytochrome P-450(CYP)2B1/2 by xylene
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Kim Ki-Woong
Heo Kyung-Hwa
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Abstract
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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 ㎎/body ㎏), X (treated with 65.9 ㎎/body ㎏) 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±0.56 ㎎ /㎖ and 0.744±0.025 nmol/㎎ protein, respectively, and they contents were significantly lower than in derived from treated groups (p<0.01). The activities of PROD and ρNPH 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±1.97 g/g creatinine and TX combined group was 2.91±1.76 g/g creatinine, but was not significant. However, amount of urinary methy hippuric acid in X single treated group (1.62±0.72 g/g creatinine) was significantly higher than TX combined group (0.93± 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.
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KEYWORD
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Toluene, Xylene, CYP2B1/2, CYP2E1, CYP dependent monooxygenase, metabolites
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