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Isothiocyanates as Inducers of Phase II DrugMetabolizing Enzyme: Involvement of Cellular Redox Alteration Yoshimasa Nakamura Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
A simple system for the rapid measurement of glutathione S-transferase placental form (GSTP1) that detoxifies polycyclic aromatic hydrocarbons using the cultured rat liver epithelial cell line, RL34 was recently developed. During the course of our studies, benzyl isothiocyanate (BITC) was isolated from papaya as a strong inducer of GST activity. BITC induced the depletion of glutathione and the generation of reactive oxygen species (ROS) in the cells. The structure-activity relationship of isothiocyanates also indicated that the ROS producing activities closely correlated with their GST inducing potencies. Moreover, the GSTP1 enhancer I (GPEI)-containing region was found to be essential for the induction of GSTP1 gene by BITC. These data suggest the involvement of redox regulation in the induction of GSTP1 by BITC.
Several lines of evidence indicate that phase II enzymes such as NAD(P)H:(quinone-acceptor) oxidoreductase (NQO1) and glutathione Stransferase (GST) play a role in the cellular detoxification of genotoxic and carcinogenic chemicals. Recently, two transgenic rodent studies clearly demonstrated that Class π GST (GSTP1), one of the GST isozymes, can profoundly alter the susceptibility to chemical carcinogenesis in mouse skin (/) and rat liver (2). The Class π rat and human GST isozymes have been
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© 2003 American Chemical Society In Food Factors in Health Promotion and Disease Prevention; Shahidi, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2003.
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shown to be highly efficient in the glutathione (GSH) conjugation of carcinogenic benz[
