Rabovsky J, Judy D J, Rodak D J, Petersen M
Environ Res. 1986 Jun;40(1):136-44. doi: 10.1016/s0013-9351(86)80089-5.
We have investigated a relationship between two detoxication systems, metabolic detoxication through the cytochrome P-450 (P-450) pathway and resistance to infection through interferon (IFN), in mice infected with influenza virus following exposure to coal dust (CD) and diesel exhaust (DE) particulates. Mice were exposed by inhalation to filtered air (FA; control), CD, or DE for 1 month and then inoculated intranasally (IN) with influenza virus. During infection, 7-ethoxycoumarin deethylase (7ECdeEt'ase) and ethylmorphine demethylase (EMdeMe'ase) (monooxygenases), and NADPH cytochrome c reductase (NADPH c red'ase) were measured in liver microsomes. Temporal patterns of enzyme activities were observed with control animals. EMdeMe'ase and NADPH c red'ase exhibited peak values at Day 4 postinfection (27.6 and 482 nmole/min/mg protein, respectively), compared to initial activities (9.1 and 307 nmole/min/mg protein, respectively). 7ECdeEt'ase activity decreased between Days 1-3 postvirus infection and thereafter returned to the original value (1.7 nmole/min/mg protein). When the mice were first exposed to CD or DE particulates for 1 month prior to influenza infection, changes in enzyme temporal patterns were observed. The increased EMdeMe'ase activity at Day 4 was not observed in mice exposed to CD and was reduced in mice exposed to DE. Preexposure to either particulate resulted in the abolition of the increased Day 4 activity of NADPH c red'ase. The 7ECdeEt'ase postinfection temporal pattern was not affected by a preexposure to either particulate. Estimates of the enzyme activities after the 1-month exposure to FA, CD, or DE but before virus infection indicated no changes due to particulate exposure alone. Under these conditions of particulate exposure and virus infection, serum IFN levels in the mice used in this study peaked at Days 4-5 and were unaffected by the 1-month preexposure to CD or DE (Hahon et al., (1985). The data suggest the relationship that exists between metabolic detoxication and resistance to infection in normal mice was altered during a short-term preexposure to CD or DE.
我们研究了在接触煤尘（CD）和柴油机尾气（DE）颗粒物后感染流感病毒的小鼠中，两种解毒系统之间的关系，即通过细胞色素P-450（P-450）途径的代谢解毒和通过干扰素（IFN）的抗感染能力。小鼠通过吸入过滤空气（FA；对照）、CD或DE 1个月，然后经鼻内（IN）接种流感病毒。在感染期间，测定肝微粒体中的7-乙氧基香豆素脱乙基酶（7ECdeEt'ase）和乙基吗啡脱甲基酶（EMdeMe'ase）（单加氧酶）以及NADPH细胞色素c还原酶（NADPH c red'ase）。观察了对照动物酶活性的时间模式。与初始活性（分别为9.1和307 nmol/min/mg蛋白质）相比，EMdeMe'ase和NADPH c red'ase在感染后第4天表现出峰值（分别为27.6和482 nmol/min/mg蛋白质）。7ECdeEt'ase活性在病毒感染后第1 - 3天之间下降，此后恢复到原始值（1.7 nmol/min/mg蛋白质）。当小鼠在流感感染前先接触CD或DE颗粒物1个月时，观察到酶时间模式的变化。在接触CD的小鼠中未观察到感染后第4天EMdeMe'ase活性增加，而在接触DE的小鼠中该活性降低。预先接触任何一种颗粒物都会导致感染后第4天NADPH c red'ase活性增加消失。感染后7ECdeEt'ase的时间模式不受预先接触任何一种颗粒物的影响。在接触FA、CD或DE 1个月但在病毒感染之前对酶活性的估计表明，仅颗粒物接触不会导致变化。在这些颗粒物接触和病毒感染的条件下，本研究中使用的小鼠血清IFN水平在第4 - 5天达到峰值，并且不受预先接触CD或DE 1个月的影响（Hahon等人，（1985年）。数据表明，在短期预先接触CD或DE期间，正常小鼠中代谢解毒与抗感染能力之间存在的关系发生了改变。
