目的:流行病学研究表明氡和香烟烟雾在诱发肺癌中相互作用,但是尼古丁对氡发出的α辐射的反应作用尚不清楚。
方法:支气管上皮BEAS-2B细胞用2μM尼古丁预处理16小时,暴露于辐射,或组合。DNA损伤,细胞和染色体改变,我们对氧化应激和炎症反应进行了评估,以研究尼古丁在调节反应中的作用.
结果:与单独使用α辐射相比,在α辐射暴露(1-2Gy)后1小时检测到较少的γH2AX灶,而单独的尼古丁没有效果。彗星试验显示,在联合暴露后,DNA断裂已经更少了,由减少的p-ATM支持,p-DNA-PK,p-p53和RAD51在1小时,与单独的α辐射相比。然而,在照射后27小时,组合组的易位频率更高。虽然尼古丁在24小时没有改变G2阻滞,它在放射后48小时协助细胞周期进展。根据细胞活力动力学和活细胞计数,组合组中的恢复速度略快。并显着使用集落形成测定。使用PU139的泛组蛋白乙酰转移酶抑制阻断了p-p53和γH2AX激活的减少,提示尼古丁诱导的组蛋白乙酰化在快速DNA修复中的作用。尼古丁对活性氧的诱导作用不大,但倾向于增加α颗粒诱导的促炎IL-6和IL-1β(4Gy)。有趣的是,尼古丁不会改变γ辐射诱导的γH2AX灶。
结论:这项研究提供了证据,表明尼古丁通过引起更快但更容易出错的修复来调节α辐射反应,以及快速恢复,这可能允许具有基因组不稳定性的细胞扩增。这些结果对估计尼古丁使用者的辐射风险具有重要意义。
OBJECTIVE: Epidemiological studies show that radon and cigarette smoke interact in inducing lung cancer, but the contribution of nicotine in response to alpha radiation emitted by radon is not well understood.
METHODS: Bronchial epithelial BEAS-2B cells were either pre-treated with 2 µM nicotine during 16 h, exposed to radiation, or the combination. DNA damage, cellular and chromosomal alterations, oxidative stress as well as inflammatory responses were assessed to investigate the role of nicotine in modulating responses.
RESULTS: Less γH2AX foci were detected at 1 h after alpha radiation exposure (1-2 Gy) in the combination group versus alpha radiation alone, whereas nicotine alone had no effect. Comet assay showed less DNA breaks already just after combined exposure, supported by reduced p-ATM, p-DNA-PK, p-p53 and RAD51 at 1 h, compared to alpha radiation alone. Yet the frequency of translocations was higher in the combination group at 27 h after irradiation. Although nicotine did not alter G2 arrest at 24 h, it assisted in cell cycle progression at 48 h post radiation. A slightly faster recovery was indicated in the combination group based on cell viability kinetics and viable cell counts, and significantly using colony formation assay. Pan-histone acetyl transferase inhibition using PU139 blocked the reduction in p-p53 and γH2AX activation, suggesting a role for nicotine-induced histone acetylation in enabling rapid DNA repair. Nicotine had a modest effect on reactive oxygen species induction, but tended to increase alpha particle-induced pro-inflammatory IL-6 and IL-1β (4 Gy). Interestingly, nicotine did not alter gamma radiation-induced γH2AX foci.
CONCLUSIONS: This study provides evidence that nicotine modulates alpha-radiation response by causing a faster but more error-prone repair, as well as rapid recovery, which may allow expansion of cells with genomic instabilities. These results hold implications for estimating radiation risk among nicotine users.