Chemoprevention of tobacco smoke-induced lung tumors by inhalation of an epigallocatechin gallate (EGCG) aerosol: a pilot study.
We investigated whether inhalation of aerosolized epigallocatechin gallate (EGCG) would prevent the development of lung tumors produced by tobacco smoke (TS). Male strain A/J mice were exposed for 5 mo, 6 h/day, 5 days/wk, to a mixture of tobacco sidestream and mainstream smoke. At the end of this exposure, 3 groups were formed: (a) mice exposed to TS and left undisturbed in air; (b) animals exposed to TS and given EGCG aerosol by nose-only inhalation for 30 min per session; and (c) animals exposed to TS and then exposed by nose-only inhalation to water aerosol without any EGCG (sham-exposed group). Three similar groups were formed from animals that previously had been kept in filtered air. In experiment 1, the EGCG concentration in the aerosol was 80 microg/L and administered 3 times a week and in experiment 2 it was 191 microg/L administered twice a week. Inhalation of EGCG did not modulate TS-induced tumorigenesis. In two accompanying positive control experiments, animals treated with the tobacco-specific carcinogen NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] were given the same EGCG or water aerosol treatment. In both experiments, EGCG aerosol significantly reduced lung tumor multiplicity by 20% to 30% However, exposure of NNK-treated animals to water solvent alone (sham exposure) produced an even greater reduction in tumor multiplicities (40%). A reduction of lung tumor multiplicities was also observed in animals exposed nose-only once or five times a week to either water aerosols or to filtered air. It is concluded that water-soluble chemopreventive agents that need to be ingested in comparatively high doses are not the most suitable candidates for administration by inhalation.
Witschi
Hanspeter
H
Center for Health and the Environment and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616, USA. hrwitschi@ucdavis.edu
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Uyeminami
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Dexter
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Raabe
Otto G
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D000336:Aerosols; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D010865:Pilot Projects; D015430:Weight Gain / Q000187:drug effects
D000336:Aerosols; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D002392:Catechin; C045651:epigallocatechin gallate