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Related Experiment Videos

Chemoprevention by isothiocyanates

S S Hecht1

  • 1American Health Foundation, Naylor Dana Institute for Disease Prevention, Division of Chemical Carcinogenesis, Valhalla, NY 10595, USA.

Journal of Cellular Biochemistry. Supplement
|January 1, 1995
PubMed
Summary

Naturally occurring isothiocyanates like phenethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC) show promise in preventing lung cancer. These compounds inhibit the metabolism of tobacco smoke carcinogens, suggesting potential for smokers.

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Area of Science:

  • Chemoprevention
  • Carcinogen Metabolism
  • Molecular Toxicology

Background:

  • Isothiocyanates are potent chemopreventive agents against various cancers.
  • Their efficacy is linked to modulating carcinogen metabolism (Phase I and II enzymes).
  • Optimal chemoprevention often requires co-administration during carcinogen exposure.

Purpose of the Study:

  • To investigate phenethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC) as lung cancer inhibitors.
  • To evaluate their efficacy against major tobacco smoke carcinogens: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BaP).
  • To explore the potential of combining PEITC and BITC for enhanced lung cancer chemoprevention.

Main Methods:

  • Rodent models (F-344 rats, A/J mice) were used to study lung tumorigenesis.
  • Specific carcinogens NNK and BaP were administered to induce lung tumors.
  • Metabolic activation pathways of NNK and BaP were analyzed in lung tissues.
  • Urinary excretion of metabolites, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide, was measured.

Main Results:

  • PEITC inhibited NNK-induced lung tumors in rats and mice.
  • BITC inhibited BaP-induced lung tumors in mice.
  • Combined PEITC and BITC treatment inhibited lung tumorigenesis induced by both NNK and BaP in mice.
  • PEITC selectively inhibited NNK metabolic activation and induced NNAL glucuronidation in rodent lungs.
  • PEITC and BITC reduced DNA adduct formation and increased carcinogen excretion at non-toxic doses.

Conclusions:

  • PEITC and BITC are effective chemopreventive agents against key tobacco smoke carcinogens in preclinical models.
  • Non-toxic doses of PEITC and BITC can inhibit carcinogen activation and carcinogenicity in lung tissue.
  • Combining PEITC and BITC offers a promising strategy for lung cancer chemoprevention in smokers by targeting multiple carcinogens.

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