Fanucchi Michelle V, Day Kimberly C, Clay Candice C, Plopper Charles G
Department of Veterinary Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Toxicol Appl Pharmacol. 2004 Nov 15;201(1):53-65. doi: 10.1016/j.taap.2004.05.002.
The postnatal period of lung development is a critical window of susceptibility to environmental toxicants, including polyaromatic hydrocarbons (PAHs) and furans. To determine whether the increased susceptibility of neonatal lung injury due to environmental toxicants is a universal response across species and also applies to nitrated compounds, adult and 7-day-old male mice and rats were given a single intraperitoneal dose (0, 12.5, 25, 50, or 100 mg/kg) of 1-nitronaphthalene and killed 24 h later. Exposure to 1-nitronaphthalene, a nitro-polyaromatic hydrocarbon, results in pulmonary lesions in both adult rats and mice, although the severity of the injury is species-specific (greater in rats than in mice). Pulmonary lesions, as assessed by quantitative histopathology, included dose-dependent vacuolization and exfoliation of both ciliated and nonciliated airway epithelial cells throughout the airway tree in both rats and mice. In both species, the 7-day-old animals were more susceptible to injury by 1-nitronaphthalene than adult animals. In contrast to adult response, neonatal mice were more susceptible to 1-nitronaphthalene-induced pulmonary injury than neonatal rats. This indicates that neonatal susceptibility to environmental pollutant-induced lung injury cannot be reliably predicted based on adult susceptibility.
肺部发育的产后阶段是对环境毒物(包括多环芳烃(PAHs)和呋喃)易感性的关键窗口期。为了确定环境毒物导致的新生儿肺损伤易感性增加是否是跨物种的普遍反应,并且是否也适用于硝化化合物,对成年和7日龄雄性小鼠及大鼠腹腔注射单次剂量(0、12.5、25、50或100 mg/kg)的1-硝基萘,24小时后处死。接触1-硝基萘(一种硝基多环芳烃)会导致成年大鼠和小鼠出现肺部病变,尽管损伤的严重程度具有物种特异性(大鼠比小鼠更严重)。通过定量组织病理学评估,肺部病变包括大鼠和小鼠气道树中整个气道的纤毛和非纤毛气道上皮细胞的剂量依赖性空泡化和脱落。在这两个物种中,7日龄动物比成年动物对1-硝基萘引起的损伤更敏感。与成年动物的反应不同,新生小鼠比新生大鼠对1-硝基萘诱导的肺损伤更敏感。这表明不能根据成年动物的易感性可靠地预测新生儿对环境污染物诱导的肺损伤的易感性。