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Inhibitory Effects of Phenetyl Isothiocyanate on N-Nitrosobenzylmethylamine Carcinogenesis in the Rat Esophagus¹

Department of Pathology, Medical College of Ohio, Toledo, Ohio 43614 [G. D. S., D. T. M., Y-H. H., E. M. D., A. J. G.], and Division of Epidemiology and Toxicology, Ohio Department of Health, Columbus, Ohio 43266 [S. A. W.]

F-344 rats fed diets containing phenethyl isothiocyanate (PEITC; 3 and 6 µmol/g diet), a naturally occurring constituent of cruciferous vegetables, before and during treatment with the carcinogen N-nitrosobenzylmethylamine (NBMA), developed 99–100% fewer esophageal tumors than NBMA-treated control rats. PEITC exhibited inhibitory effects against both preneoplastic lesions (acanthosis and hyperkeratosis, leukoplakia, leukokeratosis) and neoplastic lesions (papilloma, carcinoma). Tumors were not observed in rats treated with PEITC alone. The effects of PEITC (10, 25, 50, 100 µM) on the metabolism and DNA binding of NBMA in cultured explants of rat esophagus were also investigated. PEITC produced a marked (53–97%) dose-dependent inhibition in the binding of NBMA metabolites to DNA and in the levels of DNA methylation at the N⁷ (20–89%) and O⁶ (55–93%) positions of guanine. This isothiocyanate also reduced the metabolism of NBMA by esophageal tissues as indicated by increased amounts of unmetabolized NBMA in the medium of cultures containing PEITC. Collectively, these data indicate that PEITC is a potent inhibitor of NBMA-induced esophageal carcinogenesis in rats.

¹ This research was supported by National Cancer Institute Grants CA28950 and CA46535.

² To whom requests for reprints should be addressed, at Department of Pathology, Medical College of Ohio, Health Education Building, Room 202, P.O. Box 10008, Toledo, OH 43699.

Received 10/19/90. Accepted 2/ 6/91.

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