Carcinogenesis Advance Access originally published online on October 24, 2003
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Carcinogenesis, Vol. 25, No. 2, 197-201,
February 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Effect of chemopreventive agents on separate stages of progression of benzo[
]pyrene induced lung tumors in A/J mice
1 Department of Laboratory Medicine and Pathology and 2 Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA and 3 Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA
The effects of aerosol budesonide and dietary myo-inositol on progression of benzo[
]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 wt. 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 36 week time period. Hyperplasia first appeared
6 weeks post-carcinogen followed by adenoma at 9 weeks, then by carcinoma at 26 weeks. From this temporal sequence we determined we could test for effects of preventive agents on progression to hyperplasia by intervening at 3 weeks, for effects on progression to adenoma by intervening at 6 weeks and for effects on progression to carcinoma by intervention at 12 weeks. Intervention at 3 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 12 weeks post-carcinogen. Dietary myo-inositol failed to suppress progression from adenoma to carcinoma when started 12 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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