Cigarette-Derived Nicotine is not a Medicine

Regular smokers feel better when smoking than not smoking, and empirical studies confirm that nicotine reinstatement relieves feelings of stress, depression and anger. These acute mood changes have led to the belief that cigarette-derived nicotine can provide medicinal benefits for smokers. However, prospective studies of adolescents who take up cigarette smoking find that they report increased levels of anxiety, stress and depression. Furthermore, adults who quit smoking report enduring mood improvements. Thus the prospective data shows that the nicotine derived from cigarettes leads to heightened distress. The empirical patterns of mood change reported by regular smokers show why nicotine dependency is psychologically damaging. Regular smokers report average moods when replete with nicotine, but suffer mood deteriorations in-between cigarettes. Thus the supposed mood gains of smoking only represent the temporary relief of withdrawal symptoms. This mood relief becomes conditioned with smoke inhalation, which is why cigarettes are regarded positively by smokers. However, the repetitive experience of irritability and other abstinence symptoms in between cigarettes paradoxically causes smokers to suffer worse daily moods than non-smokers. The stronger the nicotine dependency the greater the mood decrements, helping to explain why disadvantaged individuals often smoke heavily and find quitting difficult. In conclusion, there is no empirical evidence that cigarettes provide medicinal benefits, but extensive data showing that nicotine dependency heightens psychological distress in tobacco smokers.     

Immunomodulation of dendritic cells differentiated in the presence of nicotine with lipopolysaccharide from Porphyromonas gingivalis

Tobacco smoking is a significant risk factor for periodontal diseases. Nicotine, one of the most studied constituents in cigarette smoke, is thought to modify immune responses. Dendritic cells (DCs), which are key mediators between innate and adaptive immunity, stimulate naive T cells to differentiate to effector T‐cell subsets that may be actively involved in the immunopathogenesis of periodontal diseases. In this study, we evaluated the effects of nicotine and lipopolysaccharide (LPS) from Porphyromonas gingivalis, alone and in combination, on the functions of human monocyte‐derived DCs to elucidate the mechanism of tissue destruction of smoking‐associated periodontal diseases. P. gingivalis LPS‐stimulated DCs differentiated with nicotine (NiDCs) induced lower T‐cell proliferation and human leukocyte antigen (HLA)‐DR expression, but elevated expression of programmed cell death ligand 1. Additionally, NiDCs impaired interferon‐γ production but maintained interleukin (IL)‐5 and IL‐10 production in co‐cultured T cells. Furthermore, NiDCs produced lower levels of proinflammatory cytokines compared with DCs differentiated in the absence of nicotine. Interestingly, NiDCs preferentially produced the T helper 2 (Th2)‐type chemokines macrophage chemotactic protein‐1 and macrophage‐derived chemokine. These results suggest that the presence of nicotine during differentiation of DCs modulates the immunoregulatory functions of P. gingivalis LPS‐stimulated DCs.     

Application of the buccal micronucleus cytome assay and analysis of PON1Gln192Arg and CYP2A6*9(−48T>G) polymorphisms in tobacco farmers

Tobacco is a major Brazilian cash crop. Tobacco farmers apply large amounts of pesticides to control insect growth. Workers come into contact with green tobacco leaves during the tobacco harvest and absorb nicotine through the skin. In the present study, micronucleus frequency, cell death, and the frequency of basal cells were measured in tobacco farmers using the buccal micronucleus cytome assay (BMCyt), in parallel with measurement of blood butyrylcholinesterase (BChE) and nicotine levels. Polymorphisms in PONIGln192Arg and CYP2A6*9(?48T>G) were evaluated to verify the relationship between genetic susceptibility and the measured biomarkers. Peripheral blood and buccal cell samples were collected from 106 agricultural workers, at two different crop times (during pesticide application and leaf harvest), as well as 53 unexposed controls. BMCyt showed statistically significant increases in micronuclei, nuclear buds, and binucleated cells among exposed subjects in differentiated cells, and in micronuclei in basal cells. In addition, the exposed group showed higher values for condensed chromatin, karyorrhectic, pyknotic, and karyolitic cells, indicative of cell death, and an increase in the frequency of basal cells compared to the unexposed control group. A slight difference in mutagenicity using the BMCyt assay was found between the two different sampling times (pesticide application and leaf harvest), with higher micronucleus frequencies during pesticide application. Elevated cotinine levels were observed during the leaf harvest compared to the unexposed controls, while BChE level was similar among the farmers and controls. PONIGln192Arg and CYP2A6*9(?48T>G) polymorphisms were associated with DNA damage induced by pesticides and cell death. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.