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将A/J品系小鼠暴露于香烟侧流烟雾中六个月:细胞动力学和肺癌数据。

Six-month exposure of strain A/J mice to cigarette sidestream smoke: cell kinetics and lung tumor data.

作者信息

Witschi H, Oreffo V I, Pinkerton K E

机构信息

Institute of Toxicology and Environmental Health, University of California, Davis 95616, USA.

出版信息

Fundam Appl Toxicol. 1995 Jun;26(1):32-40. doi: 10.1006/faat.1995.1072.

Abstract

Male strain A/J mice were exposed to sidestream smoke (SS) generated from burning Kentucky 1R4F reference cigarettes. Chamber concentrations were 4 mg/m3 of total suspended respirable particulate matter (TSP). Animals were exposed 6 hr a day, 5 days a week. One-week cumulative labeling indices were significantly increased in the large intrapulmonary airways during the 1st week and in the respiratory epithelium of the nasal and maxillar turbinates during the first 3 weeks of exposure and then returned to control values. Subsequently, signs of increased cell proliferation were again found in the nasal and maxillar turbinates during the 9th and 16th exposure weeks. The experiment was terminated after 6 months. The number of animals bearing lung tumors was the same in smoke-exposed as in filtered air-exposed animals as was the average number of tumors per lung. Analysis of the DNA of individual tumors obtained from exposed and control mice for K-ras mutations suggested that exon 2 might be a specific target for SS. It was concluded that (1) duration of exposure was too short or (2) concentration of TSP was too low to reveal a possible carcinogenic potential of SS in strain A/J mice or that (3) SS is not carcinogenic in strain A mice.

摘要

雄性A/J品系小鼠暴露于肯塔基1R4F参比香烟燃烧产生的侧流烟气(SS)中。实验舱内总悬浮可吸入颗粒物(TSP)浓度为4 mg/m³。动物每天暴露6小时,每周暴露5天。在暴露的第1周,肺内大气道的一周累积标记指数显著升高,在暴露的前3周,鼻腔和上颌鼻甲的呼吸上皮的一周累积标记指数也显著升高,随后恢复到对照值。随后,在暴露的第9周和第16周,鼻腔和上颌鼻甲再次出现细胞增殖增加的迹象。6个月后实验结束。暴露于烟雾中的动物和暴露于过滤空气中的动物的肺部肿瘤数量相同,每只肺的肿瘤平均数量也相同。对从暴露小鼠和对照小鼠获得的单个肿瘤的DNA进行K-ras突变分析表明,外显子2可能是侧流烟气的一个特定靶点。得出的结论是:(1)暴露时间过短或(2)TSP浓度过低,无法揭示侧流烟气在A/J品系小鼠中可能的致癌潜力,或者(3)侧流烟气在A品系小鼠中不具有致癌性。

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