Selgrade M K, Daniels M J, Jaskot R H, Robinson B L, Allis J W
Environmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
J Toxicol Environ Health. 1993 Sep;40(1):129-44. doi: 10.1080/15287399309531780.
This study assessed effects of exposure to p-xylene, a ubiquitous air pollutant, on mice infected with murine cytomegalovirus (MCMV), a mouse model for a common human virus. It was postulated that adverse health effects could occur as a result of (1) enhanced infection due to xylene-induced immune suppression, (2) increased p-xylene toxicity due to viral suppression of cytochrome P-450 (P-450), and/or (3) additive or synergistic effects on liver function due to tissue injury by both p-xylene and MCMV. Mice were exposed to filtered air, 600 or 1200 ppm p-xylene 6 h/d for 4 d and infected with a sublethal dose of MCMV after the first exposure. No deaths occurred among uninfected, p-xylene-exposed mice or infected, air-exposed mice; 34% and 0% mortality occurred respectively in infected mice exposed to 1200 and 600 ppm p-xylene. Virus titers in the liver and splenic natural killer cell activity were unaffected by exposure to 1200 ppm p-xylene. Small but significant increases in serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities, indicators of liver damage, were observed at 4 d postinfection. p-Xylene exposure had no effect on these serum enzyme activities in uninfected mice, but 1200 ppm potentiated this effect in infected mice. MCMV significantly suppressed and p-xylene significantly increased total P-450 levels in the liver, but there was no significant interaction between the two. Isozymes 1A1, 2B1/B2, and 2E1 were decreased to a similar degree, suggesting that the virus does not target specific isozymes. Enhanced mortality was not due to immune suppression. While p-xylene potentiated liver damage was caused by the virus, the magnitude of serum enzyme activities indicates that this damage was not a likely cause of death. The cause of deaths is unclear, results were consistent with the hypothesis that enhanced mortality was related to enhanced xylene toxicity due to suppression of P-450, although additive or synergistic damage to tissues other than liver cannot be ruled out.
本研究评估了暴露于普遍存在的空气污染物对二甲苯，对感染鼠巨细胞病毒（MCMV）的小鼠的影响，MCMV是一种常见人类病毒的小鼠模型。据推测，可能会由于以下原因产生不良健康影响：（1）二甲苯诱导的免疫抑制导致感染增强；（2）病毒对细胞色素P-450（P-450）的抑制导致对二甲苯毒性增加；和/或（3）对二甲苯和MCMV两者造成的组织损伤对肝功能产生相加或协同作用。将小鼠暴露于过滤空气、600或1200 ppm对二甲苯，每天6小时，持续4天，并在首次暴露后用亚致死剂量的MCMV感染。未感染且暴露于对二甲苯的小鼠或感染且暴露于空气的小鼠中均未发生死亡；暴露于1200和600 ppm对二甲苯的感染小鼠的死亡率分别为34%和0%。暴露于1200 ppm对二甲苯对肝脏中的病毒滴度和脾自然杀伤细胞活性没有影响。在感染后4天观察到血清天冬氨酸转氨酶、丙氨酸转氨酶和乳酸脱氢酶活性（肝损伤指标）有小幅但显著的增加。对二甲苯暴露对未感染小鼠的这些血清酶活性没有影响，但1200 ppm增强了感染小鼠中的这种影响。MCMV显著抑制且对二甲苯显著增加肝脏中的总P-450水平，但两者之间没有显著的相互作用。同工酶1A1、2B1/B2和2E1下降到相似程度，表明该病毒不靶向特定同工酶。死亡率增加并非由于免疫抑制。虽然对二甲苯增强的肝损伤是由病毒引起的，但血清酶活性的程度表明这种损伤不太可能是死亡原因。死亡原因尚不清楚，结果与以下假设一致，即死亡率增加与P-450受抑制导致的对二甲苯毒性增强有关，尽管不能排除对肝脏以外的组织有相加或协同损伤。
