Gunnison A F, Weideman P A, Sobo M, Koenig K L, Chen L C
Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Fundam Appl Toxicol. 1992 Apr;18(3):360-9. doi: 10.1016/0272-0590(92)90134-4.
Previous work from this laboratory demonstrated that neonatal rats and postweanling rabbits are more sensitive to ozone-induced stimulation of pulmonary arachidonic acid (AA) metabolism than are young adults (Fundam. Appl. Toxicol. 15, 779.) In the study reported here, we have extended our initial investigation to include the influence of animal age on temporal aspects of pulmonary AA metabolism and several other responses to brief exposures to 1 ppm ozone. Rats of discrete ages ranging from 13 days to 16 weeks were exposed to 1 ppm ozone or to air for 2, 4, or 6 hr. Immediately following exposure the lungs were lavaged with six consecutive volumes of phosphate-buffered saline and the acellular fluid from the first lavage volume recovered was analyzed for its content of prostaglandin E2 (PGE2), protein, and lactate dehydrogenase. Leukocytes recovered by lavage were quantitated and characterized by viability and percentage of polymorphonuclear (PMN) cells. Several lines of evidence verified that PGE2 was produced by the lung as a consequence of ozone exposure and that its concentration in the fluid from the first lavage was a reasonably good index of pulmonary AA metabolism to prostanoids. We also demonstrated that the lavage process itself stimulates the lung, resulting in increased AA metabolism to prostanoids that were recovered in the second and following lavage volumes. The time course of PGE2 production by the ozone-exposed lung varied considerably with animal age. Neonatal rats 13 days of age were the most sensitive to ozone stimulation. At 2 hr of exposure, PGE2 concentration in the first lung lavage of these animals peaked at values approximately two orders of magnitude above controls and then decreased sharply with continued exposure. Adults and older neonates (18 days of age) were much less responsive to 2-hr exposures; however, continued exposure of these rats for up to 6 hr resulted in increasing PGE2 concentration in the first lung lavage. Other responses showed various degree of age dependence. The percentage of lavaged leukocytes that were nonviable (i.e., trypan blue-positive) showed a strong inverse correlation with animal age. In 13-day-old rats that were exposed for 6 hr, the percentage of dead leukocytes reached nearly 50%. In addition, sheets or clumps of dead cells that were judged to be epithelial cells were lavaged from these animals. Conversely, 16-week-old adult males exposed to ozone for 6 hr showed little evidence of damage to cells of the respiratory tract.(ABSTRACT TRUNCATED AT 400 WORDS)
本实验室先前的研究表明，新生大鼠和断奶后的兔子比年轻成年动物对臭氧诱导的肺花生四烯酸（AA）代谢刺激更为敏感（《基础与应用毒理学》15卷，第779页）。在本文报道的研究中，我们扩展了最初的研究，纳入了动物年龄对肺AA代谢时间进程以及对短暂暴露于1 ppm臭氧的其他几种反应的影响。将年龄从13天到16周不等的大鼠暴露于1 ppm臭氧或空气中2、4或6小时。暴露后立即用连续六倍体积的磷酸盐缓冲盐水对肺进行灌洗，并分析首次灌洗回收的无细胞液中前列腺素E2（PGE2）、蛋白质和乳酸脱氢酶的含量。对灌洗回收的白细胞进行定量，并根据活力和多形核（PMN）细胞百分比进行表征。多条证据证实，PGE2是臭氧暴露后肺产生的，其在首次灌洗液中的浓度是肺AA代谢为前列腺素的一个相当好的指标。我们还证明灌洗过程本身会刺激肺，导致AA代谢为前列腺素增加，这些前列腺素在第二次及后续灌洗体积中回收。臭氧暴露肺产生PGE2的时间进程随动物年龄有很大差异。13日龄的新生大鼠对臭氧刺激最为敏感。在暴露2小时时，这些动物首次肺灌洗中的PGE2浓度峰值比对照组高出约两个数量级，然后随着持续暴露急剧下降。成年大鼠和较大的新生大鼠（18日龄）对2小时暴露的反应要小得多；然而，这些大鼠持续暴露长达6小时会导致首次肺灌洗中PGE2浓度增加。其他反应表现出不同程度的年龄依赖性。灌洗的无活力白细胞（即台盼蓝阳性）百分比与动物年龄呈强烈负相关。在暴露6小时的13日龄大鼠中，死亡白细胞百分比接近50%。此外，从这些动物中灌洗出了被判定为上皮细胞的成片或成团的死亡细胞。相反，暴露于臭氧6小时的16周龄成年雄性大鼠几乎没有呼吸道细胞受损的迹象。（摘要截取自400字）
