| First Author | Miller MS | Year | 2013 |
| Journal | Carcinogenesis | Volume | 34 |
| Issue | 2 | Pages | 319-24 |
| PubMed ID | 23104176 | Mgi Jnum | J:194128 |
| Mgi Id | MGI:5470372 | Doi | 10.1093/carcin/bgs332 |
| Citation | Miller MS, et al. (2013) Chemoprevention by N-acetylcysteine of low-dose CT-induced murine lung tumorigenesis. Carcinogenesis 34(2):319-24 |
| abstractText | Data from the National Lung Screening Trial suggested that annual computed tomography (CT) screening of at-risk patients decreases lung cancer mortality by 20%. We assessed the effects of low-dose CT radiation in mice exposed to 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) to mimic the effects of annual CT screening in heavy smokers and ex-smokers. A/J mice were treated at 8 weeks with NNK followed 1 week later by 4 weekly doses of 0, 10, 30 or 50 mGy of whole-body CT and euthanized 8 months later. Irradiated mice exhibited significant 1.8- to 2-fold increases in tumor multiplicity in males (16.1 +/- 0.8 versus 9.1 +/- 1.5 tumors per mouse; P < 0.0001) and females (21.6 +/- 0.8 versus 10.5 +/- 1.4 tumors per mouse; P < 0.0001), respectively, compared with unirradiated mice with no dose effect observed; female mice exhibited higher sensitivity to radiation exposure than did males (P < 0.0001). Similar results were obtained when tumor area was determined. To assess if the deleterious effects of radiation could be prevented by antioxidants, female mice were fed a diet containing 0.7% N-acetylcysteine (NAC) starting 3 days prior to the first CT exposure and continuing for a total of 5 weeks. NAC prevented CT induced increases in tumor multiplicity (10.5 +/- 1.2 versus 20.7 +/- 1.5 tumors per mouse; P < 0.0001) back to levels seen in NNK/unirradiated mice (10.5 +/- 1.2). Our data suggest that exposure of sensitive populations to CT radiation increases the risk of tumorigenesis, and that antioxidants may prevent the long-term carcinogenic effects of low-dose radiation exposure. This would allow annual screening with CT while preventing the potential long-term toxicity of radiation exposure. |
