Witschi Hanspeter, Espiritu Imelda, Ly Man, Uyeminami Dale, Morin Dexter, Raabe Otto G
Center for Health and the Environment and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Inhal Toxicol. 2004 Oct-Nov;16(11-12):763-70. doi: 10.1080/08958370490490400.
We investigated whether inhalation of aerosolized epigallocatechin gallate (EGCG) would prevent the development of lung tumors produced by tobacco smoke (TS). Male strain A/J mice were exposed for 5 mo, 6 h/day, 5 days/wk, to a mixture of tobacco sidestream and mainstream smoke. At the end of this exposure, 3 groups were formed: (a) mice exposed to TS and left undisturbed in air; (b) animals exposed to TS and given EGCG aerosol by nose-only inhalation for 30 min per session; and (c) animals exposed to TS and then exposed by nose-only inhalation to water aerosol without any EGCG (sham-exposed group). Three similar groups were formed from animals that previously had been kept in filtered air. In experiment 1, the EGCG concentration in the aerosol was 80 microg/L and administered 3 times a week and in experiment 2 it was 191 microg/L administered twice a week. Inhalation of EGCG did not modulate TS-induced tumorigenesis. In two accompanying positive control experiments, animals treated with the tobacco-specific carcinogen NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] were given the same EGCG or water aerosol treatment. In both experiments, EGCG aerosol significantly reduced lung tumor multiplicity by 20% to 30% However, exposure of NNK-treated animals to water solvent alone (sham exposure) produced an even greater reduction in tumor multiplicities (40%). A reduction of lung tumor multiplicities was also observed in animals exposed nose-only once or five times a week to either water aerosols or to filtered air. It is concluded that water-soluble chemopreventive agents that need to be ingested in comparatively high doses are not the most suitable candidates for administration by inhalation.
我们研究了吸入雾化表没食子儿茶素没食子酸酯（EGCG）是否能预防烟草烟雾（TS）诱发的肺部肿瘤。将雄性A/J品系小鼠每周5天、每天6小时暴露于烟草侧流烟雾和主流烟雾的混合物中，持续5个月。暴露结束后，分为3组：（a）暴露于TS且置于空气中不受干扰的小鼠；（b）暴露于TS并通过仅经鼻吸入EGCG气雾剂，每次30分钟的动物；（c）暴露于TS，然后仅经鼻吸入不含任何EGCG的水汽雾剂的动物（假暴露组）。从先前饲养在过滤空气中的动物中形成了3个类似的组。在实验1中，气雾剂中EGCG浓度为80μg/L，每周给药3次；在实验2中，其浓度为191μg/L，每周给药2次。吸入EGCG并未调节TS诱导的肿瘤发生。在两个伴随的阳性对照实验中，用烟草特异性致癌物NNK [4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮]处理的动物接受相同的EGCG或水汽雾剂处理。在两个实验中，EGCG气雾剂均使肺肿瘤数量显著减少20%至30%。然而，仅用溶剂（假暴露）处理NNK处理的动物，肿瘤数量减少幅度更大（40%）。每周仅经鼻暴露一次或五次于水汽雾剂或过滤空气中的动物，肺肿瘤数量也有所减少。得出的结论是，需要较高剂量摄入的水溶性化学预防剂并非最适合经吸入给药的候选药物。
