Chen Jinguo, Higby Richard, Tian Defa, Tan Duanjun, Johnson Michael D, Xiao Yingxian, Kellar Kenneth J, Feng Shibao, Shields Peter G
Lombardi Comprehensive Cancer Center, Georgetown University, Georgetown University Medical Center, Washington, DC 20057-1465, USA.
Toxicology. 2008 Jul 30;249(2-3):194-203. doi: 10.1016/j.tox.2008.05.009. Epub 2008 May 24.
Low-nicotine and nicotine-free cigarettes are commercially available under the brand-name Quest. Some consumers may believe that these are safer cigarettes, and they may smoke more cigarettes or inhale more smoke to compensate for low nicotine yields. Thus, we have studied the toxicological effects of these two cigarettes and compared them with the Kentucky reference cigarette 2R4F. Also, the availability of nicotine-free cigarettes allows for the assessing the role of nicotine in cigarette smoke. In addition to nicotine, some tobacco-specific nitrosamines, aldehydes, and volatile organic compounds were also reduced in the Quest cigarettes compared to the 2R4F. However, aromatic amines were higher in the nicotine-free compared with low nicotine cigarettes. The Ames test revealed that cigarette smoke condensates from the nicotine-free (CSC-F), low nicotine (CSC-L) and 2R4F (CSC-R) cigarettes had a similar mutagenic potency. Exposure to any CSC caused a similar dose-dependent LDH leakage from normal human bronchial epithelial cells. However, CSC-F had more inhibitory effects on the cell growth than CSC-L and CSC-R. Adding nicotine to the CSC-F attenuated this inhibition. Both Quest CSCs decreased gap junction intercellular communication and caused cell cycle arrest. CSC exposure increased cytoplasmic nucleosomes, sub-G1/G0 population and apoptotic comet tails. Proapoptotic protein Bax increased independent of p53 induction after exposure to CSC-F. In conclusion, these studies are not consistent with a perception that low-nicotine or nicotine-free cigarettes may have less toxicity in human cells. Nicotine, as it exists in CSC, attenuates cytotoxicity possibly in part through inhibition of apoptotic pathways.
低尼古丁和无尼古丁香烟以“探索”（Quest）品牌在市场上销售。一些消费者可能认为这些香烟更安全，他们可能会吸更多香烟或吸入更多烟雾以弥补低尼古丁含量。因此，我们研究了这两种香烟的毒理学效应，并将它们与肯塔基参考香烟2R4F进行了比较。此外，无尼古丁香烟的可得性使得我们能够评估尼古丁在香烟烟雾中的作用。与2R4F相比，“探索”香烟中除尼古丁外，一些烟草特有的亚硝胺、醛类和挥发性有机化合物的含量也有所降低。然而，无尼古丁香烟中的芳香胺含量高于低尼古丁香烟。艾姆斯试验表明，无尼古丁香烟（CSC-F）、低尼古丁香烟（CSC-L）和2R4F香烟（CSC-R）的香烟烟雾冷凝物具有相似的诱变潜力。暴露于任何一种CSC都会导致正常人支气管上皮细胞出现类似的剂量依赖性乳酸脱氢酶泄漏。然而，CSC-F对细胞生长的抑制作用比CSC-L和CSC-R更强。向CSC-F中添加尼古丁可减弱这种抑制作用。两种“探索”香烟的CSC都会减少间隙连接细胞间通讯并导致细胞周期停滞。CSC暴露会增加细胞质核小体、亚G1/G0期细胞群和凋亡彗星尾。暴露于CSC-F后，促凋亡蛋白Bax增加，且与p53诱导无关。总之，这些研究结果与低尼古丁或无尼古丁香烟对人体细胞毒性可能较小的观念不一致。CSC中的尼古丁可能部分通过抑制凋亡途径来减弱细胞毒性。
