Cell proliferation kinetics and genotoxicity in lymphocytes of smokers living in mexico city

Abstract

<jats:p> Genotoxicity caused by tobacco smoke was assessed in peripheral blood lymphocytes of smokers living in Mexico City by determining sister chromatid exchange (SCE), cell proliferation kinetics (CPK), replication index (RI) and mitotic index (MI). Nicotine levels, and its major metabolite cotinine, were also estimated in urine samples using gas-chromatography-mass spectrometry to quantify smoking intensity. The outcome of the analysis and the comparison of the 77-smoker group with a non-smoking control group showed that moderate and heavy smokers exhibited significant differences ( P &lt; 0.001 and P &lt; 0.05, respectively) in CPK, with an underlying delay in the cellular cycle; similarly, RI was significantly different in these groups ( P &lt; 0.001 and P &lt; 0.0001, respectively). There were significant correlations ( P &lt; 0.05) between age and number of years the subject had been smoking, as well as between RI and nicotine and cotinine levels and between CPK (M1, M2 and M3) and nicotine and cotinine levels. Smokers were classified for the analysis according to the nicotine levels (it is in relation to number of cigarettes smoked per day) found in urine (ng/mL) as: light (10—250), moderate (251—850) and heavy (851—4110). Significant differences in CPK were found ( P &lt; 0.05) between moderate and heavy smokers and non-smokers. Significant differences in RI were found between moderate ( P &lt; 0.001) and heavy smokers ( P &lt; 0.0001) and non-smokers, but not for the light smoking group. MI was determined in 57 of the smokers, whereas SCE frequency was only recorded in 34 smokers. Both parameters yielded no significant differences, nor correlations with any of the assessed variables. In conclusion, cytokinetic and cytostatic effects were mainly detected in heavy and moderate smokers. Cell cycle delay and RI decrease were found in all `healthy' smokers. The nicotine and cotinine exposure (causing oxidative damage to DNA) may have implications in the decrease in cell replication due to direct damage to DNA and/or a decrease in the DNA repair mechanisms. Alternatively, nicotine and cotinine may possibly induce apoptosis. Human &amp; Experimental Toxicology (2007) 26, 715—722 </jats:p>

Adaptive response: some underlying mechanisms and open questions

“…The increased frequencies of chromosomal aberrations and sister chromatid exchanges in radiation workers could indicate a cumulative effect of low level chronic exposure to ionizing radiation, pointing to the relevance of conducting cytogenetic analysis in addition to physical dosimetry in such cases (Cardoso et al, 2001). Although cytokinetic and cytostatic effects have been detected in heavy and moderate smokers (Calderón-Ezquerro et al, 2007), smoking habits may or may not affect the genotoxic effect of chronic radiation exposure (Maffei et al, 2002;Hadjidekova et al, 2003;Sari-Minodier et al, 2007).…”

Evaluation of the genotoxicity and cytotoxicity in the general population in Turkey by use of the cytokinesis-block micronucleus cytome assay

“…Moreover, in one study the MN frequency was reported to be significantly lower in the smoker group than in the controls [19]. However, several studies have indicated that individuals who smoke a larger number of cigarettes per day (≥30 cigarettes per day) have a significantly increased MN frequency [3,9,18,22].…”

“…Many studies have shown that there is an increase in MN frequency with age [3,[9][10][11][12][13][14][15][16][17][18][19], although others have not shown any correlation between MN frequency and age [16,18,20]. As for the role of gender, most studies have reported that MN frequency in females is higher than that in males [3,9,12,14,[16][17][18][19]21], whereas in others the gender had no effect [16,18,20].…”

“…As for the role of gender, most studies have reported that MN frequency in females is higher than that in males [3,9,12,14,[16][17][18][19]21], whereas in others the gender had no effect [16,18,20].…”

Polymorphisms of DNA Repair Pathway Genes and Cigarette Smoking in Relation to Susceptibility to Large Artery Atherosclerotic Stroke among Ethnic Chinese in Taiwan

“…Although the mechanism underlying cigarette smoke-induced cerebrovascular injury regarding to stroke remains unclear, cigarette constituents are known to activate reactive oxygen species (ROS) on DNA damage within the vascular wall, leading to premature vascular aging and endothelial dysfunction 3,5,6) . A direct causality in which exposure to cigarette smoke results in elevated levels of DNA aberrations in various human cell types, including fibroblasts, lymphocytes and endothelial cells has been shown in earlier reports 7,8) . Recently, accumulating evidence from cohort studies revealed that the increased risk of stroke is generally associated with smoking 9,10) .…”