Carcinogenesis Advance Access published online on October 24, 2003
Carcinogenesis, doi:10.1093/carcin/bgg196
© 2003 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
Received 5 June 2003
; revised 2 October 2003
; accepted 12 October 2003
The effects of aerosol budesonide and dietary myo-inositol on progression of benzo[
Effect of chemopreventive agents on separate stages of progression of benzo[
]pyrene induced lung tumors in A/J mice
2 Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA
3 Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA
]pyrene (B[]P) induced carcinogenesis were studied in A/J mouse lung. First, we determined when to intervene in the carcinogenesis process by exposing several animals to B[]P at 100 and 150 mg/kg of body weight. Groups of these animals were necropsied from 1 to 36 weeks post carcinogen. The presence of different categories of lung tumors was noted over the thirty six week time period. Hyperplasia first appeared about six weeks post carcinogen followed by adenoma at nine weeks, then by carcinoma at twenty six weeks. From this temporal sequence we determined we could test for effects of preventive agents on progression to hyperplasia by intervening at three weeks, for effects on progression to adenoma by intervening at six weeks and for effects on progression to carcinoma by intervention at twelve weeks. Intervention at three weeks post carcinogen with aerosolized budesonide delayed both hyperplasia and adenoma formation. Once hyperplasia appeared in budesonide treated animals, however, it increased at the same rate as in control animals, indicating a delay in progression. Progression from adenoma to carcinoma was reduced when budesonide was given twelve weeks post carcinogen. Dietary myo-inositol failed to suppress progression from adenoma to carcinoma when started twelve weeks post carcinogen. In summary, budesonide is a chemopreventive agent that has inhibitory effects on B[]P induced carcinogenesis of the lung in A/J mice at all stages of progression from hyperplasia formation to cancer.
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