Chemoprevention of pulmonary carcinogenesis by brief exposures to aerosolized budesonide or beclomethasone dipropionate and by the combination of aerosolized budesonide and dietary myo-inositol.
This investigation is part of an effort to develop chemoprevention for carcinogenesis of the lung. It focuses on the efficacy of low doses of synthetic glucocorticoids administered either as single agents or in combination with a second compound, myo-inositol. Glucocorticoids are potent inhibitors of carcinogenesis. The use of low doses is important to avoid potential side-effects. The synthetic glucocorticoid budesonide, administered by aerosol for 20 s three times a week, was studied to determine its effects on benzo[a]pyrene-induced pulmonary adenoma formation in female A/J mice. Two dose levels were employed, 10 and 25 microg/kg body wt. The lower dose produced a 34% reduction in lung tumor formation and the higher dose level a 60% reduction in lung tumors. In additional groups of mice, the effects of 0.3% myo-inositol added to the diet was found to reduce pulmonary tumor formation by 53%. The two agents given in combination resulted in a greater inhibition of lung tumor formation than either by itself. Budesonide at 10 microg/kg body wt plus 0.3% myo-inositol reduced the number of tumors by 60% and budesonide at 25 microg/kg body wt plus 0.3% myo-inositol reduced lung tumor formation by 79%. To determine whether a glucocorticoid other than budesonide would have inhibitory effects in this experimental model, beclomethasone dipropionate administered by aerosol for 20 s three times a week was studied as a single agent and showed almost identical inhibitory properties to budesonide. The doses of the glucocorticoids calculated on a daily basis are within the range of those used widely for control of chronic allergic respiratory diseases in the human. The capacity of low doses of inhaled glucocorticoids to prevent pulmonary neoplasia and the enhancement of this preventive effect by myo-inositol, an essentially non-toxic compound, are findings that should encourage further work to evaluate the applicability of these agents to the prevention of neoplasia of the lung in the human.
Wattenberg
L W
LW
Department of Laboratory Medicine and Pathology and College of Pharmaceutics, School of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. watte002@maroon.tc.umn.edu
Wiedmann
T S
TS
Estensen
R D
RD
Zimmerman
C L
CL
Galbraith
A R
AR
Steele
V E
VE
Kelloff
G J
GJ
D000236:Adenoma / Q000517:prevention & control*; D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001507:Beclomethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001564:Benzo(a)pyrene; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002273:Carcinogens; D004032:Diet; D004357:Drug Synergism; D005260:Female; D007294:Inositol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008805:Mice, Inbred A; D010316:Particle Size
D000336:Aerosols; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D001564:Benzo(a)pyrene; D007294:Inositol; D019819:Budesonide; D001507:Beclomethasone