Witschi H, Espiritu I, Peake J L, Wu K, Maronpot R R, Pinkerton K E
University of California, Davis, Department of Molecular Biosciences, School of Veterinary Medicine, USA.
Carcinogenesis. 1997 Mar;18(3):575-86. doi: 10.1093/carcin/18.3.575.
Male strain A/J mice were exposed for 6 h a day, 5 days a week to environmental tobacco smoke (ETS) generated from Kentucky 1R4F reference cigarettes. Chamber concentrations were 87 mg/m3 of total suspended particulate matter (TSP), 246 p.p.m. of CO and 16 mg/m3 of nicotine. After 5 months, 33% of the ETS exposed and 11% of the control animals had one or several lung tumors; the difference was statistically not significant. A second group of animals exposed for 5 months to ETS was allowed to recover for another 4 months in filtered air. When they were killed, 85% of the ETS animals had lung tumors (average number per lung: 1.4 +/- 0.2), whereas in the control group 38% had lung tumors (average number of lung tumors in all animals 0.5 +/- 0.2). The differences in tumor incidence and multiplicity were statistically significant. More than 80% of all tumors were adenomas, the rest adenocarcinomas. When animals were pretreated with a carcinogen, lung tumor multiplicity was lower in the ETS exposed animals after 5 months compared with controls injected with a carcinogen and kept in air. However, after an additional 4 month recovery period in air, lung tumor multiplicities were the same in ETS plus carcinogen exposed mice as in carcinogen-treated air-exposed controls. Histopathologic and morphometric analysis of the lung tissue failed to reveal any differences between ETS exposed and control animals. However, immediately after ETS exposure, immunohistochemistry revealed increased staining for CYP1A1 in airway epithelia and lung parenchyma; following recovery in air, the staining disappeared again. Analysis of cell kinetics showed an initial burst of increased DNA synthesis in the epithelial cells of the airways and a smaller early positive response in the parenchyma. Feeding of butylated hydroxytoluene during ETS exposure did not modulate lung tumor development. It was concluded that ETS is a pulmonary carcinogen in strain A/J mice.
雄性A/J品系小鼠每周5天、每天暴露于肯塔基1R4F参考香烟产生的环境烟草烟雾（ETS）中6小时。实验室内总悬浮颗粒物（TSP）浓度为87毫克/立方米，一氧化碳浓度为246 ppm，尼古丁浓度为16毫克/立方米。5个月后，33%暴露于ETS的动物和11%的对照动物出现一个或多个肺部肿瘤；差异无统计学意义。第二组暴露于ETS 5个月的动物在过滤空气中再恢复4个月。处死时，85%暴露于ETS的动物患有肺部肿瘤（每只肺平均数量：1.4±0.2），而对照组中38%患有肺部肿瘤（所有动物肺部肿瘤平均数量0.5±0.2）。肿瘤发生率和多发性的差异具有统计学意义。所有肿瘤中超过80%为腺瘤，其余为腺癌。当动物用致癌物预处理后，暴露于ETS的动物在5个月后肺部肿瘤多发性低于注射致癌物并饲养在空气中的对照组。然而，在空气中额外恢复4个月后，暴露于ETS加致癌物的小鼠肺部肿瘤多发性与致癌物处理的空气暴露对照组相同。对肺组织的组织病理学和形态计量学分析未能揭示暴露于ETS的动物与对照动物之间的任何差异。然而，在暴露于ETS后立即进行免疫组织化学分析，发现气道上皮和肺实质中CYP1A1染色增加；在空气中恢复后，染色再次消失。细胞动力学分析显示气道上皮细胞中DNA合成最初有一阵增加，实质中有较小的早期阳性反应。在暴露于ETS期间喂食丁基羟基甲苯并未调节肺部肿瘤的发展。得出的结论是，ETS是A/J品系小鼠的肺部致癌物。
