Differential response of four human livers to modulation of phase II enzyme systems by the chemopreventive phytochemical phenethyl isothiocyanate.
A principal mechanism of the chemopreventive activity of isothiocyanates is detoxification of the genotoxic metabolites of chemical carcinogens through up-regulation of enzymes such as quinone reductase and the glutathione-S-transferases. In this study we report, for the first time, the potential of the aromatic isothiocyanate, phenethyl isothiocyanate (PEITC) to modulate these enzymes in human liver from four donors, in comparison with rat liver. Precision-cut human and rat liver slices were incubated with PEITC at concentrations that can be achieved in plasma following dietary intake. Glutathione-S-transferase activity increased in rat slices whereas in human slices activity rose only in three of the four donors. At the protein level, a marked rise in GSTα was seen in one of the human donors whereas much less pronounced elevation was noted in the other three. Quinone reductase activity doubled in rat liver slices incubated with PEITC, and was accompanied by an increase in protein expression. Only in one of the human donors was activity and expression of quinone reductase elevated. These studies illustrate that there are very pronounced differences in the response of human liver to PEITC, indicating that the chemopreventive effect of isothiocyanates may not be manifested in all individuals.
Konsue
Nattaya
N
Molecular Toxicology Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
Ioannides
Costas
C
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D004137:Dinitrochlorobenzene / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009578:Nitrobenzenes / Q000378:metabolism; D009924:Organ Culture Techniques; D009994:Osmolar Concentration; D011808:Quinone Reductases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D015854:Up-Regulation / Q000187:drug effects*
D016588:Anticarcinogenic Agents; D004137:Dinitrochlorobenzene; D007527:Isoenzymes; D017879:Isothiocyanates; D009578:Nitrobenzenes; C058305:phenethyl isothiocyanate; C028328:1,2-dichloro-4-nitrobenzene; D011808:Quinone Reductases; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione