Chen K C
J Appl Toxicol. 1986 Aug;6(4):259-62. doi: 10.1002/jat.2550060406.
The potential for aryl hydrocarbon hydroxylate (AHH) induction by inhaled diesel particles was assessed by intratracheal administration. Benzo[a]pyrene, (B[a]P) a reference compound, or an extract of particles, dissolved in gelatin-saline solution was administered to Fischer 344 rats at several dose levels. Twenty-four hours after administration of B[a]P or diesel particulate extract, the AHH activity increased in a dose-response manner in the lung, but not in liver. The maximum increase in the AHH activity in the lung was observed 12 h after intratracheal instillation of B[a]P (5 mg/kg), and the levels remained elevated for seven days. The AHH activity in the liver reached the maximum 24 h after the administration, and returned rapidly to control values. In contrast, intratracheal instillation of diesel particulate extract resulted in a significant increase of AHH activity in the lungs only after doses greater than 6 mg kg-1. The activity, however, declined rapidly and returned to control values within 75 h. The liver AHH activity in this instance, remained unchanged throughout the experimental period. These data indicate that in the lung, hydrocarbons extracted from diesel particles are weak enzyme inducers and exposure to these compounds by intratracheal administration did not result in AHH induction in the liver. The results suggest that doses higher than those normally expected from occupational exposures will be required to induce AHH activity in organs examined.
通过气管内给药评估吸入柴油颗粒诱导芳烃羟化酶(AHH)的潜力。将参考化合物苯并[a]芘(B[a]P)或溶解于明胶 - 盐溶液中的颗粒提取物,以几种剂量水平给予Fischer 344大鼠。给予B[a]P或柴油颗粒提取物24小时后,肺中AHH活性呈剂量反应性增加,但肝脏中未增加。气管内滴注B[a]P(5mg/kg)后12小时观察到肺中AHH活性的最大增加,且该水平在七天内保持升高。肝脏中的AHH活性在给药后24小时达到最大值,并迅速恢复到对照值。相比之下,仅在剂量大于6mg kg-1后,气管内滴注柴油颗粒提取物才导致肺中AHH活性显著增加。然而,该活性迅速下降并在75小时内恢复到对照值。在这种情况下,整个实验期间肝脏的AHH活性保持不变。这些数据表明,在肺中,从柴油颗粒中提取的碳氢化合物是弱酶诱导剂,通过气管内给药接触这些化合物不会导致肝脏中AHH的诱导。结果表明,需要高于职业暴露通常预期剂量才能在检查的器官中诱导AHH活性。