Modulation by Phenethyl Isothiocyanate and Budesonide of Molecular and Histopathologic Alterations Induced by Environmental Cigarette Smoke in Mice
Modulation by Phenethyl Isothiocyanate and Budesonide of Molecular and Histopathologic Alterations Induced by Environmental Cigarette Smoke in Mice
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DOI：
10.1158/1940-6207.capr-08-0235
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发表时间：
2009-06-01
影响因子：
3.3
通讯作者：
De Flora, Silvio
中科院分区：
文献类型：
--
作者：
D'Agostini, Francesco;Mastracci, Luca;De Flora, Silvio
我们发现，围产期涉及核苷酸修饰和小鼠肺中基因的过度表达，这促使我们评估，当小鼠出生后立即开始暴露于香烟烟雾中时，小鼠是否会变得更容易受到香烟的影响。我们之前的研究表明，主流香烟烟雾对新生小鼠来说是一种很强的致癌物质。进一步，我们发现，从出生开始，小鼠暴露在环境香烟烟雾(ECS)中，会导致各种中间生物标志物的变化。然而，在接触ECS 4个月后，在过滤空气中恢复7个月后，肺肿瘤产率相当低。在本研究中，我们评估了糖皮质激素布地奈德和膳食剂苯乙基异硫氰酸酯对暴露于ECS 9个月和恢复2个月的小鼠的保护作用。断奶后，暴露于ECS的小鼠从出生起就经历了各种分子和细胞遗传学终点的变化，出生11个月后，它们出现了明显的组织病理学变化，如肺炭疽、肺气肿、出血区、肺泡细支气管化、支气管增生和良恶性肿瘤。在相同条件下暴露于ECS的大坝中，致癌反应不那么明显。断奶后每天与饮食一起服用异硫氰酸苯乙酯和布地奈德都可以减轻ECS相关生物标志物的几个变化，并适度保护肺部免受组织病理学变化的影响，包括肿瘤。因此，尽管没有主流香烟烟雾暴露小鼠的生物测定那么有效，但新生小鼠的模型适用于评估ECS的致癌性和化学预防药物对其调节作用。
Our discovery that the perinatal period involves nucleotide modifications and gene overexpression in mouse lung prompted us to evaluate whether mice may become more susceptible to cigarette smoke when exposure starts immediately after birth. We previously showed that mainstream cigarette smoke is a quite potent carcinogen in neonatal mice. Further on, we showed that exposure of mice to environmental cigarette smoke (ECS), starting at birth, results in alterations of a variety of intermediate biomarkers. However, after 4 months of exposure to ECS followed by 7 months of recovery in filtered air, the lung tumor yield was rather low. In the present study, we evaluated the protective effects of the glucocorticoid budesonide and of the dietary agent phenethyl isothiocyanate in mice exposed to ECS for 9 months followed by 2 months of recovery. After weanling, the mice exposed to ECS since birth underwent a variety of alterations of molecular and cytogenetical end points, and 11 months after birth, they exhibited significant histopathologic changes, such as pulmonary anthracosis, emphysema, hemorrhagic areas, alveolar bronchiolarization, bronchial hyperplasia, and tumors, both benign and malignant. The carcinogenic response was less evident in dams exposed to ECS under identical conditions. Both phenethyl isothiocyanate and budesonide, administered daily with the diet after weanling, attenuated several alterations of ECS-related biomarkers and moderately protected the lungs from histopathologic alterations, including tumors. Thus, although not as efficiently as the bioassay in mainstream cigarette smoke-exposed mice, the model in neonatal mice is suitable to evaluate both ECS carcinogenicity and its modulation by chemopreventive agents.