Abstract
The effects of phenthyl isothiocyanate(PEIFTC) on xenobiotic metabolizing enzymes and cell kinetics in the target organs for Ν-nirtosobis(2-oxopropyl) amine(BOP)-tumorigenicity were investigated in female Syrian golden hamsters in order to gain the mechanistic insigths into the chemopreventive action of PEITS against BOP-initiated lung and pancreatic carcinogenesis in hamsters. Hamsters were given BOP subcuteneo-usly(s.c.) and/or PEITC by gavage 2h prior to the BOP treatment. Eight and 24h after the PEITC administration, animals were sacrificed for analyzing P450 isoenzymes, glutathine(GSH), glutathione S-transferase(GST) and cell kinetics. The PEITC pretreatment significantly reduced the hepatic P450 isoenzume levels such as CYP2B1 and DYP1A1 which were significantly increased by the BOP treatment. However, PEITC did not affect the CYP levels in the pancreas and lung. Interestingly, the PEITC pretreatment rather lowered the heparic GST and GSH levels, regradless of BOP administration. Proliferating cell nuclear antigen(PCNA)- labeling indices were dose dependently decreased by PEITC in the pancreas acini and ducts, bronchioles, and renal tubules in which the cell replication was significantly affected by BOP. These results thus suggest that PEITC exerts the chemopreventive effects in hamsters by influencing xenobiotic matabolizing phase I enzymes in the liver and regulating cell kinetics in the target organs.