Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
Mutagenesis. 2011 Mar;26(2):295-301. doi: 10.1093/mutage/geq092. Epub 2010 Nov 2.
The primary aim of the study was to investigate the impact of tar and nicotine contents of cigarettes on chromosomal damage in oral mucosa cells of smokers. We monitored the effect of smoking different cigarette types (i.e., of ultralight filter, light filter, medium filter and unfiltered cigarettes) on induction of nuclear anomalies including micronuclei (MN), broken eggs (BE), binucleates (BN), condensed chromatin (CC), karyorrhexis (KR), karyolysis (KL) and pyknosis (P) in exfoliated buccal cells. The cells were collected from 83 healthy heavy smokers (n=15-25/group) consuming a similar number of cigarettes (26-33) per day and from never smokers as controls (n=20). The frequencies of KR, CC, KL, BE and BN were increased significantly only in smokers of medium (MF) and non-filtered (NF) types of cigarettes while MN levels were only elevated (p < 0.0001) in the group that smoked NF cigarettes. Since BN and BE were increased (p < 00001) as a consequence of exposure to lower levels of toxic constituents in tobacco, it suggests that these endpoints, which both reflect DNA damage, are more sensitive than MN, which is the only parameter scored in most earlier studies. The induction of MN, BN, KR and KL increased significantly with daily tar exposure and decreased simultaneously with daily nicotine uptake (in all cases, P was < 0.0001). These findings also suggest that nicotine potentially protects cells against DNA reactive carcinogens contained in tobacco smoke although earlier in vitro and animal studies showed that the alkaloid induces DNA damage per se. A significant inverse correlation between the frequencies of endpoints such as cells with MN (- 1.56), MN (-1.69), BN (-1.36), KR (-1.10) and KL (-1.87) with the nicotine levels in cigarettes was found. However, this observation requires further verification by a controlled intervention study. In case it can be substantiated it will have an impact on the ongoing discussion of the health risks associated with nicotine replacement therapy.
本研究的主要目的是调查香烟中的焦油和尼古丁含量对吸烟人群口腔黏膜细胞染色体损伤的影响。我们监测了不同类型香烟（即超淡过滤、淡过滤、中过滤和无过滤香烟）对诱导核异常的影响，包括微核（MN）、破碎卵（BE）、双核（BN）、浓缩染色质（CC）、核破裂（KR）、核溶解（KL）和固缩（P）。细胞取自 83 名健康重度吸烟者（n=15-25/组），他们每天吸烟 26-33 支，另有 20 名从不吸烟者作为对照。只有吸食中滤嘴（MF）和无滤嘴（NF）香烟的吸烟者的 KR、CC、KL、BE 和 BN 频率显著增加，而仅 NF 香烟组的 MN 水平升高（p<0.0001）。由于 BN 和 BE 的增加（p<00001）是由于接触烟草中较低水平的有毒成分所致，这表明这些终点比仅在大多数早期研究中评分的 MN 更敏感，MN 反映了 DNA 损伤。MN、BN、KR 和 KL 的诱导与每日焦油暴露显著相关，与每日尼古丁摄取同时减少（在所有情况下，P<0.0001）。这些发现还表明，尼古丁可能保护细胞免受烟草烟雾中含有的 DNA 反应性致癌物质的侵害，尽管早期的体外和动物研究表明，生物碱本身会引起 DNA 损伤。MN （-1.56）、MN （-1.69）、BN （-1.36）、KR （-1.10）和 KL （-1.87）等终点的频率与香烟中尼古丁水平之间存在显著的负相关。然而，这一观察结果需要通过对照干预研究进一步验证。如果可以证实，这将对正在进行的与尼古丁替代疗法相关的健康风险的讨论产生影响。
