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

• Published in: Carcinogenesis (New York) Vol. 25; no. 2; pp. 197 - 201
• Main Authors: Estensen, R. D., Jordan, M. M., Wiedmann, T. S., Galbraith, A. R., Steele, V. E., Wattenberg, L. W.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-02-2004; Oxford Publishing Limited (England)
• Subjects: Adenoma - physiopathology; Adenoma - prevention & control; Aerosols; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - therapeutic use; B[α]P; Benzo(a)pyrene - toxicity; benzo[α]pyrene; Biological and medical sciences; Budesonide - administration & dosage; Budesonide - therapeutic use; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - toxicity; Chemical agents; Disease Progression; Female; geometric standard deviation; GSD; Hyperplasia - prevention & control; Inositol - therapeutic use; Lung - pathology; Lung Neoplasms - physiopathology; Lung Neoplasms - prevention & control; mass median aerodynamic diameter; Medical sciences; Mice; Mice, Inbred A; MMAD; Neoplasm Staging; Tumors; Prevention; Vertebrata; Chemotherapy; Mammalia; Mouse; Lung; Rodentia; Tumor progression; Malignant tumor; Anticarcinogen; Bronchopulmonary
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/bgg196

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.