Calderón-Ezquerro C, Sánchez-Reyes A, Sansores R H, Villalobos-Pietrini R, Amador-Muñoz O, Guerrero-Guerra C, Calderón-Segura M E, Uribe-Hernández R, Gómez-Arroyo S
Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México.
Hum Exp Toxicol. 2007 Sep;26(9):715-22. doi: 10.1177/0960327107083451.
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 < 0.001 and P < 0.05, respectively) in CPK, with an underlying delay in the cellular cycle; similarly, RI was significantly different in these groups (P < 0.001 and P < 0.0001, respectively). There were significant correlations (P < 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 < 0.05) between moderate and heavy smokers and non-smokers. Significant differences in RI were found between moderate (P < 0.001) and heavy smokers (P < 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.
通过测定姐妹染色单体交换（SCE）、细胞增殖动力学（CPK）、复制指数（RI）和有丝分裂指数（MI），评估了居住在墨西哥城的吸烟者外周血淋巴细胞中烟草烟雾引起的遗传毒性。还使用气相色谱-质谱法估计了尿液样本中的尼古丁水平及其主要代谢物可替宁，以量化吸烟强度。对77名吸烟者组与非吸烟对照组的分析结果及比较表明，中度和重度吸烟者在CPK方面表现出显著差异（分别为P < 0.001和P < 0.05），细胞周期存在潜在延迟；同样，这些组的RI也有显著差异（分别为P < 0.001和P < 0.0001）。年龄与受试者吸烟年限之间、RI与尼古丁和可替宁水平之间以及CPK（M1、M2和M3）与尼古丁和可替宁水平之间存在显著相关性（P < 0.05）。根据尿液中发现的尼古丁水平（与每天吸烟支数相关，单位为ng/mL），将吸烟者分为：轻度（10 - 250）、中度（251 - 850）和重度（851 - 4110）进行分析。中度和重度吸烟者与非吸烟者在CPK方面存在显著差异（P < 0.05）。中度吸烟者（P < 0.001）和重度吸烟者（P < 0.0001）与非吸烟者在RI方面存在显著差异，但轻度吸烟组未出现此差异。在其中57名吸烟者中测定了MI，而仅在34名吸烟者中记录了SCE频率。这两个参数均未产生显著差异，也与任何评估变量无相关性。总之，细胞动力学和细胞抑制作用主要在重度和中度吸烟者中检测到。在所有“健康”吸烟者中均发现细胞周期延迟和RI降低。尼古丁和可替宁暴露（对DNA造成氧化损伤）可能因对DNA的直接损伤和/或DNA修复机制的降低而导致细胞复制减少。或者，尼古丁和可替宁可能诱导细胞凋亡。
