Journal Article

Chemoprevention by <i>N</i>-acetylcysteine of low-dose CT-induced murine lung tumorigenesis

Mark Steven Miller, Joseph E. Moore, Matthew C. Walb, Nancy D. Kock, Albert Attia, Scott Isom, Jennifer E. McBride and Michael T. Munley

in Carcinogenesis

Volume 34, issue 2, pages 319-324
Published in print February 2013 | ISSN: 0143-3334
Published online October 2012 | e-ISSN: 1460-2180 | DOI:
Chemoprevention by N-acetylcysteine of low-dose CT-induced murine lung tumorigenesis

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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.

Journal Article.  5987 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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