Journal Article

Effect of chemopreventive agents on separate stages of progression of benzo[α]pyrene induced lung tumors in A/J mice

R. D. Estensen, M. M. Jordan, T. S. Wiedmann, A. R. Galbraith, V. E. Steele and L. W. Wattenberg

in Carcinogenesis

Volume 25, issue 2, pages 197-201
Published in print February 2004 | ISSN: 0143-3334
Published online February 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg196
Effect of chemopreventive agents on separate stages of progression of benzo[α]pyrene induced lung tumors in A/J mice

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The effects of aerosol budesonide and dietary myo-inositol on progression of benzo[α]pyrene (B[α]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[α]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[α]P induced carcinogenesis of the lung in A/J mice at all stages of progression from hyperplasia formation to cancer.

Keywords: B[α]P, benzo[α]pyrene; GSD, geometric standard deviation; MMAD, mass median aerodynamic diameter

Journal Article.  3823 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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