TY - JOUR
T1 - Induction of hepatic cytochrome P450 isozymes, benzo(a)pyrene metabolism and DNA binding following exposure to polycyclic aromatic hydrocarbon residues generated during repeated fish fried oil in rats
AU - Pandey, Manoj K.
AU - Yadav, Sanjay
AU - Parmar, Devendra
AU - Das, Mukul
N1 - Funding Information:
The authors are grateful to the director, ITRC, for his keen interest in this present study. One of us (MKP) is thankful to Council of Scientific and Industrial Research (CSIR), New Delhi, for the award of Senior Research Fellowship. Financial assistance of Technology Mission of Oil seeds, Pulses and Maize (TMOP and M), New Delhi, is gratefully acknowledged. The manuscript is ITRC communication #2392.
PY - 2006/6/1
Y1 - 2006/6/1
N2 - In the present study the effect of repeated fish fried oil (RFFO) and its extract (RFFE) on hepatic cytochrome P450 (CYP) isozymes, benzo(a)pyrene (BP) metabolism and DNA adduct formation was undertaken. HPLC analysis of RFFO showed the presence of several polycyclic aromatic hydrocarbons. CYP in microsomes from control and RFFO-treated animals showed a peak at 450 nm; however, a shift of 2 nm in the SORET region along with significant induction was observed in microsomes prepared from 3-methylcholanthrene (MC)- and RFFE-treated animals. Activities of hepatic ethoxyresorufin-O-deethylase, methoxyresorufin-O-deethylase, aryl hydrocarbon hydroxylase and erythromycin-N-demethylase were found to be significantly (P < 0.05) induced following exposure of RFFE, whereas none of these enzymes were altered in RFFO-treated group. Immunoblot analysis revealed that RFFE and MC were potent inducers of CYP1A1, 1A1/2 and 3A1 isozymes, where as RFFO showed no change in these protein levels. RT-PCR analysis showed induction of cDNA of CYP1A1 and CYP3A1 by RFFE treatment. Hepatic microsomes prepared from RFFE exposed animals enhanced BP metabolism with a concomitant increase in the relative proportion of BP 7,8-diol. Hepatic microsomes prepared from animals pretreated with RFFE and MC significantly enhanced the binding of [3H]-BP to calf thymus DNA. The overall results suggest that exposure to RFFE may induce hepatic CYP isozymes thereby producing enhanced reactive metabolites with a potential to bind with DNA that may result in cancer.
AB - In the present study the effect of repeated fish fried oil (RFFO) and its extract (RFFE) on hepatic cytochrome P450 (CYP) isozymes, benzo(a)pyrene (BP) metabolism and DNA adduct formation was undertaken. HPLC analysis of RFFO showed the presence of several polycyclic aromatic hydrocarbons. CYP in microsomes from control and RFFO-treated animals showed a peak at 450 nm; however, a shift of 2 nm in the SORET region along with significant induction was observed in microsomes prepared from 3-methylcholanthrene (MC)- and RFFE-treated animals. Activities of hepatic ethoxyresorufin-O-deethylase, methoxyresorufin-O-deethylase, aryl hydrocarbon hydroxylase and erythromycin-N-demethylase were found to be significantly (P < 0.05) induced following exposure of RFFE, whereas none of these enzymes were altered in RFFO-treated group. Immunoblot analysis revealed that RFFE and MC were potent inducers of CYP1A1, 1A1/2 and 3A1 isozymes, where as RFFO showed no change in these protein levels. RT-PCR analysis showed induction of cDNA of CYP1A1 and CYP3A1 by RFFE treatment. Hepatic microsomes prepared from RFFE exposed animals enhanced BP metabolism with a concomitant increase in the relative proportion of BP 7,8-diol. Hepatic microsomes prepared from animals pretreated with RFFE and MC significantly enhanced the binding of [3H]-BP to calf thymus DNA. The overall results suggest that exposure to RFFE may induce hepatic CYP isozymes thereby producing enhanced reactive metabolites with a potential to bind with DNA that may result in cancer.
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U2 - 10.1016/j.taap.2005.09.013
DO - 10.1016/j.taap.2005.09.013
M3 - Article
C2 - 16263147
AN - SCOPUS:33646557614
VL - 213
SP - 126
EP - 134
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 2
ER -