Effect of chemopreventive agents on separate stages of progression of benzo[alpha]pyrene induced lung tumors in A/J mice.
The effects of aerosol budesonide and dietary myo-inositol on progression of benzo[alpha]pyrene (B[alpha]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[alpha]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 approximately 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[alpha]P induced carcinogenesis of the lung in A/J mice at all stages of progression from hyperplasia formation to cancer.
Estensen
R D
RD
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. esten001@umn.edu
Jordan
M M
MM
Wiedmann
T S
TS
Galbraith
A R
AR
Steele
V E
VE
Wattenberg
L W
LW
D000236:Adenoma / Q000503:physiopathology / Q000517:prevention & control*; D000336:Aerosols; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity*; D018450:Disease Progression; D005260:Female; D006965:Hyperplasia / Q000517:prevention & control; D007294:Inositol / Q000627:therapeutic use; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008805:Mice, Inbred A; D009367:Neoplasm Staging
D000336:Aerosols; D000893:Anti-Inflammatory Agents; D002273:Carcinogens; D001564:Benzo(a)pyrene; D007294:Inositol; D019819:Budesonide