title: Toxicological analysis of low-nicotine and nicotine-free cigarettes.
abstract: 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.
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Georgetown University Medical Center, Washington, DC 20057-1465, USA.
authors.forename: Jinguo
authors.initials: J
authors.lastname: Chen
authors.forename: Richard
authors.initials: R
authors.lastname: Higby
authors.forename: Defa
authors.initials: D
authors.lastname: Tian
authors.forename: Duanjun
authors.initials: D
authors.lastname: Tan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Johnson
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Xiao
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Kellar
authors.forename: Shibao
authors.initials: S
authors.lastname: Feng
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology; D002450:Cell Communication / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D054351:Electrical Synapses / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009152:Mutagenicity Tests; D009538:Nicotine / Q000032:analysis / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000032:analysis / Q000633:toxicity*; D009707:Nucleosomes / Q000187:drug effects; D012015:Reference Standards; D012906:Smoke / Q000009:adverse effects / Q000032:analysis; D012907:Smoking / Q000009:adverse effects*; D013778:Tetrazolium Salts / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D062789:Tobacco Products
chemical_list: C476329:2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt; D018722:Nicotinic Agonists; D009707:Nucleosomes; D012906:Smoke; D013778:Tetrazolium Salts; D051028:bcl-2-Associated X Protein; D009538:Nicotine; D007770:L-Lactate Dehydrogenase