Structure–Activity Relationships and Organ Specificity in the Induction of GST and NQO1 by Alkyl-Aryl Isothiocyanates

Purpose To compare the ability of alkyl-aryl isothiocyanates (ITCs) to increase the activities of the Phase 2 detoxification enzymes NAD[P]H:quinone acceptor oxidoreductase 1 (NQO1) and glutathione S -transferases (GST) in rat tissues in vivo and in cells in vitro . Materials and Methods Twelve alkyl-aryl ITCs and the fully-reduced derivative of benzyl ITC (cyclohexylmethyl ITC) were administered to rats each day for 5 days. The animals were then killed and organs harvested. The ITCs were also evaluated in a bladder cell line in culture. The activities of NQO1 and GST in the organs and cells were measured. Results In vivo , the organ most susceptible to the inductive activity of the ITCs was the urinary bladder, with α-methylbenzyl ITC and cyclohexylmethyl ITC being the most effective. Inductive activity in the bladder in vivo did not, however, correlate with that in bladder cells in vitro . Conclusions Induction of Phase 2 enzymes increases resistance to chemical carcinogenesis. ITCs could therefore be valuable chemopreventative agents, and the specificity of these substances toward the urinary bladder suggest that they could be particularly useful for protecting against bladder cancer. In this regard, α-methylbenzyl ITC and cyclohexylmethyl ITC could be especially valuable.