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Title: Modulation of carcinogen metabolism by benzyl isothiocyanate
Author: Arya, Nlin
ISNI:       0000 0001 3430 0632
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2008
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Precision-cut rat liver slices were incubated with various concentrations of benzyl isothiocyanate (BITC) (0-25 uM) for 24 hours. BITC decreased the dealkylation of ethoxy-(EROD) and methoxyresorufin (MROD) but increased CYP1A1/2 apoprotein levels; in vitro studies confirmed that it is mechanism-based inhibitor. BITC decreased both dealkylation of pentoxyresorufin (PROD) and CYP2B1 apoprotein levels but there was no effect on 7-benzyloxyquinoline (7-BQ) metabolism and CYP3A apoprotein levels. In the case of Phase II enzyme systems, BITC increased epoxide hydrolase and GST activity and a similar rises was observed in protein levels, no change was observed in NADPH: quinone oxidoreductase (NQO1). In in vivo studies, rats were fed diets supplemented with BITC, equivalent to doses of 0-50 mg/kg for 2 weeks. BITC increased EROD, MROD, PROD and 7-BQ metabolism and CYP1A1, 1A2, 2B1, and 3A apoprotein levels in the liver but not in the lung. When Phase II enzymes were modulated, BITC increased activities and protein levels of epoxide hydrolase only in the liver, whereas GST in both the liver and the lung were elevated. NQO1 was not modulated. Treatment with BITC failed to influence the metabolism of 2-amino-3-methylimidazo[4,5-f quinoline (IQ) as exemplified by the excretion of mutagens in the urine. The effect of BITC on the detoxification pathways of IQ was monitored using LC/MS. Treatment with BITC or phenethyl isothiocyanate (PEITC) in the diet for 2 weeks increased IQ 5-O-glucuronide and IQ 5-O-sulphate excretion. Treatment with high doses of BITC and PEITC 24 hours prior to IQ administration, also increased IQ 5-0-glucuronide and IQ 5-O-sulphate excretion. This effect was not observed when using sulforaphane or erucin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available