Evaluation of isothiocyanates as potent inducers of carcinogen-detoxifying enzymes in the urinary bladder: Critical nature of in vivo bioassay

Rex Munday, Yuesheng Zhang, Jed W. Fahey, Hillary E. Jobson, Christine M. Munday, Jun Li, Katherine K. Stephenson

Research output: Contribution to journalArticle

Abstract

Deficiency of carcinogen-detoxifying phase 2 enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase I (NQOI), increases bladder cancer risk in humans. We report that several isothiocyanates (ITCs) that have not been previously examined, I-methylbutyl ITC in particular, potently and preferentially induce both GST and NQOI in the rat bladder. Comparison of 25 ITCs that are closely related in chemical structures showed that a 3-5-carbon aliphatic side chain with a methyl group attached to the alpha carbon was crucial for maximal inducer activity in the bladder. Surprisingly, cell-based bioassays failed to predict the phase 2 enzyme-inducing activity of the ITCs in the bladder. Furthermore, although ITCs are principally metabolized in vivo to dithiocarbamates (DTCs), which are believed to serve as the carriers of ITCs and are rapidly eliminated and concentrated in the urine, the total urinary levels of ITC plus DTC did not correlate with the degree of GST and NQOI induction by the ITCs in the bladder of rats. Thus, several underappreciated ITCs are exceedingly potent inducers of GST and NQOI in the rat bladder but were predicted neither by in vitro bioassays of phase 2 enzyme induction nor by their appearance or concentration in urine in vivo.

Original languageEnglish (US)
Pages (from-to)223-231
Number of pages9
JournalNutrition and Cancer
Volume54
Issue number2
DOIs
StatePublished - Sep 7 2006

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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