Chemoprevention of tobacco smoke-induced lung tumors by inhalation of an epigallocatechin gallate (EGCG) aerosol: a pilot study

Inhal Toxicol. Oct-Nov 2004;16(11-12):763-70. doi: 10.1080/08958370490490400.

Abstract

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.

MeSH terms

  • Aerosols
  • Animals
  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / therapeutic use*
  • Carcinogens / toxicity*
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Catechin / therapeutic use*
  • Lung / pathology
  • Lung Neoplasms / chemically induced*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Male
  • Mice
  • Mice, Inbred A
  • Pilot Projects
  • Tobacco / toxicity*
  • Weight Gain / drug effects

Substances

  • Aerosols
  • Anticarcinogenic Agents
  • Carcinogens
  • Catechin
  • epigallocatechin gallate