Neutrophil activation in smokers

Smoking and elevated leukocyte counts are risk factors for cardiovascular disease. Experimental studies suggest that leukocyte activation may be a requirement for certain cardiovascular complications. Clinical studies have demonstrated activated leukocytes in the peripheral blood of stroke victims. Accordingly, neutrophil activation in unseparated whole blood of smokers as well as naive neutrophils of non-smokers exposed to plasma of smokers was investigated. Both spontaneous Superoxide formation as determined by nitroblue tetrazolium reduction, as well as pseudopod formation, are significantly elevated in autologous neutrophils of smokers. The surface expression of CD 18 and L-selectin on autologous circulating neutrophils of smokers is not significantly different from non-smoker controls. In contrast, incubation of naive neutrophils with smoker plasma leads to significantly higher levels of Superoxide formation, pseudopod formation, and L-selectin shedding, compared with non-smoker plasma, suggesting that the plasma of smokers contains a transferable factor which causes leukocyte activation. The results indicate that analysis of blood samples from large peripheral veins may not accurately reflect leukocyte activation in the circulation since activated leukocytes have a higher probability to be trapped in the microcirculation.     

Self-titration by cigarette smokers

An 11-week crossover study was carried out in which 12 subjects smoked high-nicotine (1·84 mg standard yield) and low-nicotine (0·6 mg) cigarettes after an initial period of smoking their usual brands with a medium-nicotine yield (mean 1·4 mg). Plasma and urine nicotine concentrations, carboxyhaemoglobin (COHb) concentration, puffing behaviour, 24-hour cigarette consumption, and butt nicotine content were measured. The changes in plasma nicotine and blood COHb concentrations showed that the smokers compensated for about two-thirds of the difference in standard yields when switched to either high- or low-nicotine cigarettes. Thus, compared with the medium-nicotine brand, the intake of nicotine and carbon monoxide was only about 10% higher when subjects smoked the high-nicotine cigarettes, which had a standard yield 30-40% higher than the medium brands; and only about 15% lower when they smoked the low-nicotine cigarettes, which had a standard yield about 50% lower than the medium brands. But nicotine content and urine nicotine concentrations followed a similar pattern. Changes in puffing behaviour and in 24-hour cigarette consumption were only slight.The results show clear evidence of both upward and downward self-titration of nicotine and carbon monoxide (and tar) intakes when smokers change to cigarettes with standard yields that differ over the range studied.     

Deception among smokers.

Subjects in two different clinical trials who had been advised to stop smoking were asked if they had done so. Some 22% of subjects (11 out of 51) in the first trial and 40% (33/82) in the second trial who said they had stopped smoking were found to have raised carboxyhaemoglobin concentrations. Deception appears to be common in people trying to stop smoking.     

Chromosomal aberrations in heavy smokers

Summary Lymphocyte chromosomes from 20 heavy smokers were analyzed from 48-h whole blood cultures for the frequency of dicentric chromosomes, ring chromosomes, and chromatid translocations. Compared to controls, these exchange type aberrations occurred more frequently in the smokers.     

Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer

Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11–2.59,p = 0.01), whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25–0.65,p<0.001 and OR = 0.51;95%CI = 0.33–0.78,p = 0.002 respectively). In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His), SULT1A1 213GG (Arg/Arg) or AA (His/His) and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33–10.55,p = 0.006), whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg) and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15–7.51,p = 0.01). MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His) and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His) with testing balance accuracy (TBA) of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with SULT1A1 Arg213His and EPHX1 Tyr113His in smokers and SULT1A1 Arg213His with GSTP1 Ile105Val and CYP1A1*2C in nonsmokers. These results identified distinct gene-gene and gene environment interactions in smokers and non-smokers, which confirms the importance of multifactorial interaction in risk assessment of lung cancer.     

Sister chromatid exchange in cigarette smokers

Summary The incidence of sister chromatid exchanges in smokers and nonsmokers was investigated. There was no difference in the SCE rate between smokers and nonsmokers, nor was there any difference between heavy (>10 per day) and light (<10 per day) smokers.     

Genetic risk assessment in hookah smokers

The genotoxic effect of hookah smoke was investigated on somatic chromosomes of 35 occupationally nonexposed male hookah smokers. These were compared with an equal number of nonsmokers matched with respect to age, sex, drug intake, if any, and socio-economic status. The mitotic index (MI), chromosomal aberrations (CA), sister chromatid exchanges (SCE) and satellite associations (SA) were analysed. All the parameters showed a significant increase (p < 0.01) in the smokers compared with control individuals, viz MI, 3.88-5.41; CA, 0.94-2.22; SCE, 3.59-5.66; and SA, 5.2-8.65. A distinct time and dose effect relationship was observed. Hookah smoke is thus, both clastogenic and genotoxic for human beings.