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Eur J Cancer. 2009 May;45(7):1257-64. doi: 10.1016/j.ejca.2008.10.035. Epub 2009 Feb 28.

beta-Carotene promotes the development of NNK-induced small airway-derived lung adenocarcinoma.

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  • 1Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA.



beta-Carotene has shown cancer-preventive effects in preclinical studies while increasing lung cancer mortality in clinical trials. We have shown that beta-carotene stimulates cAMP signalling in vitro. Here, we have tested the hypothesis that beta-carotene promotes the development of pulmonary adenocarcinoma (PAC) in vivo via cAMP signalling.


PAC was induced in hamsters with the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), followed by beta-carotene for 1.5 years. Incidence, multiplicity and size of lung tumours were recorded, and phosphorylated CREB and ERK1/2 in tumour cells were determined by Western blots. Cyclic AMP in blood cells was analysed by immunoassays, retinoids in serum and lungs by HPLC.


beta-Carotene increased lung tumour multiplicity, lung tumour size, blood cell cAMP, serum and lung levels of retinoids and induced p-CREB and p-ERK1/2 in lung tumours.


Our data suggest that beta-carotene promotes the development of PAC via increased cAMP signalling.

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