Lung tumor development in mice exposed to tobacco smoke and fed beta-carotene diets.
Lung tumor development in mice exposed to tobacco smoke and fed beta-carotene diets.
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暴露于烟草烟雾并喂食β-胡萝卜素饮食的小鼠发生肺肿瘤。
DOI：
10.1093/toxsci/69.1.23
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Witschi,Hanspeter
中科院分区：
文献类型：
--
作者：
Obermueller-Jevic,UteC;Espiritu,Imelda;Corbacho,AnaM;Cross,CarrollE;Witschi,Hanspeter
在人体临床试验中发现，假定的化学预防药物β-胡萝卜素不仅不能保护活跃的吸烟者免受烟草烟雾的致癌作用，而且实际上增加了他们患肺癌的风险。在临床前动物研究中，β-胡萝卜素对一些化学诱导的癌症有效，但对呼吸道肿瘤无效。我们将雄性A/J小鼠暴露于总悬浮颗粒物浓度为140 mg/m~3的烟草烟雾中，每天6小时，每周5天，连续4个月或5个月，然后在空气中恢复4或5个月，或9个月不恢复期间。在0.005、0.05和0.5%的烟草烟雾暴露期间或之后，将β-胡萝卜素以明胶小珠的形式添加到AIN-93G饮食中。在补充饲料的动物中，血浆和肺中β-胡萝卜素的水平高于喂食对照饲料的动物。暴露在烟草烟雾中会增加而不是降低血浆β-胡萝卜素水平，但对肺水平没有显著影响。9个月后，测定肺肿瘤的多发性和发病率。烟草烟雾增加了肺癌的多发性和发病率，但β-胡萝卜素在所有暴露条件下都不能调节肿瘤的发展。因此，在烟草烟雾致癌模型中进行的动物研究将预测，补充β-胡萝卜素对现在或以前的吸烟者没有任何有益的影响，但无法预测肺癌风险的增加。
In human clinical trials it was found that the putative chemopreventive agent β-carotene not only failed to protect active smokers against the carcinogenic action of tobacco smoke, but actually increased their risk of developing lung cancer. In preclinical animal studies, β-carotene had been effective against some chemically induced cancers, but not against tumors in the respiratory tract. We exposed male strain A/J mice to tobacco smoke at a concentration of 140 mg/m3of total suspended particulate matter, 6 h a day, 5 days a week, for either 4 or 5 months, followed by a recovery period in air for 4 or 5 months, or for 9 months without recovery period. β-carotene was added in the form of gelatin beadlets to the AIN-93G diet either during or following tobacco smoke exposure at concentrations of 0.005, 0.05 and 0.5%. In the supplement-fed animals, plasma and lung levels of β-carotene were higher than they were in animals fed control diets. Exposure to tobacco smoke increased rather than decreased plasma β-carotene levels, but had no significant effect on lung levels. After 9 months, lung tumor multiplicities and incidence were determined. Tobacco smoke increased both lung tumor multiplicities and incidences, but β-carotene failed to modulate tumor development under all exposure conditions. Animal studies in a model of tobacco smoke carcinogenesis would thus have predicted the absence of any beneficial effects of β-carotene supplementation in current or former smokers, but would have failed to anticipate the increase in lung cancer risk.