Elovaara E, Zitting A, Nickels J, Aitio A
Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland.
Arch Toxicol. 1987;61(1):21-6. doi: 10.1007/BF00324543.
Rats were exposed to 0, 75, 150 or 300 ppm (1 ppm = 1 cm3/m3 = 4.35 mg/m3) m-xylene for 24 h and then killed. In the lungs, the cytochrome P-450 decreased to 45, 13 and 20% of the control value with the increasing exposure intensity and the activity of 7-ethoxycoumarin O-deethylase to 70, 27 and 14%, respectively. The activity of epoxide hydrolase increased slightly after exposures both at 150 (1.6-fold) and 300 cm3/m3 (1.4-fold), while the other measured drug-metabolizing enzyme activities showed no consistent changes. The non-protein sulfhydryl group content of the lungs was not affected. The concentrations of m-xylene in blood indicated that the solvent uptake increased in the different exposure groups more than expected, based on atmospheric concentrations alone. Morphologic studies of the lungs with scanning electron microscopy showed no apparent changes after exposure to 300 cm3/m3 or after a high oral dose (2 ml/kg/day, 3 days). Inhalation exposure to m-xylene for 5 weeks (7 h/day, 4 days/week) at a concentration of 300 ppm lowered the contents of cytochrome P-450 in rat lungs to 65% and the activity of 7-ethoxycoumarin O-deethylase to 41% without any other marked effects on the other drug-metabolizing enzymes or on the levels of non-protein sulfhydryl groups. In this study, the selective destruction of cytochrome P-450 in rat lung could be shown both after acute and subacute exposures and at concentrations low enough to warrant occupational concern.
将大鼠暴露于浓度为0、75、150或300 ppm（1 ppm = 1 cm³/m³ = 4.35 mg/m³）的间二甲苯中24小时，然后处死。在肺中，随着暴露强度增加，细胞色素P - 450降至对照值的45%、13%和20%，7 - 乙氧基香豆素O - 脱乙基酶的活性分别降至对照值的70%、27%和14%。在暴露于150 cm³/m³（1.6倍）和300 cm³/m³（1.4倍）后，环氧化物水解酶的活性略有增加，而其他所测药物代谢酶的活性未显示出一致变化。肺中非蛋白巯基含量未受影响。血液中间二甲苯的浓度表明，基于仅大气浓度，不同暴露组中溶剂摄取量的增加超过预期。用扫描电子显微镜对肺进行形态学研究显示，暴露于300 cm³/m³后或高口服剂量（2 ml/kg/天，3天）后无明显变化。以300 ppm的浓度吸入暴露于间二甲苯5周（每天7小时，每周4天），大鼠肺中细胞色素P - 450的含量降至65%，7 - 乙氧基香豆素O - 脱乙基酶的活性降至41%，而对其他药物代谢酶或非蛋白巯基水平没有任何其他明显影响。在本研究中，无论是急性还是亚急性暴露后，以及在低至足以引起职业关注的浓度下，均可显示大鼠肺中细胞色素P - 450的选择性破坏。
