Naphthalene cytotoxicity of differentiating Clara cells in neonatal mice
Naphthalene cytotoxicity of differentiating Clara cells in neonatal mice
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DOI：
10.1006/taap.1997.8119
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发表时间：
1997-05-01
影响因子：
3.8
通讯作者：
Plopper, CG
中科院分区：
文献类型：
--
作者：
Fanucchi, MV;Buckpitt, AR;Plopper, CG
许多生物活性肺毒物造成的选择性Clara细胞损伤被认为是由于在分化的Clara细胞中发现了高水平的激活酶。最近的一项研究发现，当Clara细胞P450活性较低时，新生兔对Clara细胞毒物4-异丙醇的易感性升高。为了确定另一物种（小鼠）中的分化的Clara细胞是否更容易受到不同生物活性Clara细胞毒物（萘）的伤害，我们分别给成年、产后14天（DPN）和7DPN雄性小鼠单次腹腔注射（25、50或100 mg/kg）萘，并在24小时后杀死它们。通过定量组织病理学评估，上皮损伤包括细胞肿胀、空泡化和脱落。在最低剂量（25 mg/kg）下，7DPN小鼠细支气管上皮受到严重损伤。25 mg/kg剂量对14DPN小鼠细支气管上皮造成中度损伤；50和100 mg/kg组损伤程度最大。在50 mg/kg剂量下，成年小鼠发生轻度细支气管上皮损伤，在100 mg/kg剂量下发生中度损伤。在近端支气管，7DPN小鼠的上皮仅在100 mg/kg时出现损伤迹象。各组小鼠支气管上皮均未见损伤。7DPN和14DPN小鼠离体远端气道比成年小鼠离体远端气道对萘暴露更敏感。尽管P450活性水平较低，但新生小鼠的分化Clara细胞比成年小鼠的分化Clara细胞更容易受到生物活性细胞毒物萘的损伤。(C) 1997学术出版社。
Selective Clara cell injury produced by many bioactivated lung toxicants is thought to result from high levels of activating enzymes found in differentiated Clara cells. A recent study found an elevated susceptibility to the Clara cell toxicant 4-ipomeanol in neonatal rabbits when Clara cell P450 activity is low, To determine whether differentiating Clara cells in another species (mouse) are more susceptible to injury by a different bioactivated Clara cell toxicant (naphthalene), adult, 14-day postnatal (DPN) and 7DPN male mice were given a single intraperitoneal dose (25, 50, or 100 mg/kg) of naphthalene and killed 24 hr later. Epithelial damage, as assessed by quantitative histopathology, included cellular swelling, vacuolization, and exfoliation. In 7DPN mice, bronchiolar epithelium was severely injured at the lowest dose of naphthalene tested, 25 mg/kg. Bronchiolar epithelium in 14DPN mice was moderately injured at 25 mg/kg; injury severity was greatest at 50 and 100 mg/kg. Minimal bronchiolar epithelial injury occurred in adult mice at 50 mg/kg and moderate injury at 100 mg/kg. In proximal bronchi, epithelium of 7DPN mice showed signs of injury only at 100 mg/kg. Bronchial epithelium of adult mice was not injured at any dose. Isolated distal airways from 7DPN and 14DPN mice were more sensitive to naphthalene exposure than isolated distal airways from adult mice. Despite the low levels of P450 activity, differentiating Clara cells in neonatal mice are more susceptible to injury by the bioactivated cytotoxicant naphthalene than are differentiated Clara cells in adult mice. (C) 1997 Academic Press.