Nicotine interacts with DNA lesions induced by alpha radiation which may contribute to erroneous repair in human lung epithelial cells

• Published in: Ecotoxicology and environmental safety Vol. 284; p. 117009
• Main Authors: Boroumand, Nadia, Baghdissar, Carol, Elihn, Karine, Lundholm, Lovisa
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2024; Elsevier
• Subjects: Chromosomal aberration; DNA damage; DNA repair; Nicotine; Radiation; Radon; Chromosomal aberration; Radon; DNA repair; DNA damage; Radiation; Nicotine
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.117009

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. 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. 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. 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. •Nicotine and alpha radiation interact at the level of DNA damage.•Nicotine induces a more rapid recovery of lung BEAS-2B cells.•An increased risk of erroneous repair is demonstrated in the presence of nicotine.•Nicotine use and radon exposure needs consideration concerning lung cancer risk.