EFFECT OF PHENETHYL ISOTHIOCYANATE ON MICROSOMAL N-NITROSODIMETHYLAMINE METABOLISM AND OTHER MONOOXYGENASE ACTIVITIES

被引：89

作者：

ISHIZAKI, H ^{[1
]}

BRADY, JF ^{[1
]}

NING, SM ^{[1
]}

YANG, CS ^{[1
]}

机构：

[1] RUTGERS STATE UNIV,COLL PHARM,DEPT CHEM BIOL & PHARMACOGNOSY,PISCATAWAY,NJ 08855

来源：

XENOBIOTICA | 1990年 / 20卷 / 03期

关键词：

D O I：

10.3109/00498259009046845

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. Phenethyl isothiocyanate (PEITC), a dietary compound derived from cruciferous vegetables, has previously been shown to decrease N-nitrosodimethylamine (NDMA)-induced methylation of hepatic DNA, apparently by inhibition of microsomal activation of the procarcinogen. 2. Using hepatic microsomes from acetone-treated rats, PEITC exhibited competitive inhibition of NDMA demethylase activity with an apparent Ki of 1 μm. In studies using a two-stage incubation protocol, the inhibition by PEITC was time- and metabolism-dependent. 3. Using control rat liver microsomes, PEITC selectively inhibited P450 IIE1-mediated NDMA-demethylase activity as compared to the demethylation of benzpheta-mine and ethylmorphine. 4. Pretreatment of rats with a single oral dose of PEITC (1 mmol/kg body wt) 24 h before killing caused a marked decrease in hepatic NDMA demethylase activity, but an 11-fold increase in 7-pentoxyresorufin O-dealkylase activity. These trends agreed with immunoblot analysis which indicated that PEITC was a suppressor of P450 IIE1 but an inducer of P450 IIB1. 5. The selective inhibition of P450 IIE1 activity and suppression of its level in microsomes indicates a role for PEITC as a chemopreventive agent against toxic or carcinogenic metabolites of this isozyme. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

引用

页码：255 / 264

页数：10

共 47 条

[11]

Jakoby W. B., 1980, ENZYMATIC BASIS DETO, V1, P135

[12] CARBON TETRACHLORIDE-INDUCED LIPID-PEROXIDATION DEPENDENT ON AN ETHANOL-INDUCIBLE FORM OF RABBIT LIVER MICROSOMAL CYTOCHROME-P-450 [J].

JOHANSSON, I ;

INGELMANSUNDBERG, M .

FEBS LETTERS, 1985, 183 (02) :265-269

[13] HYDROXYLATION OF ACETONE BY ETHANOL-INDUCED AND ACETONE-INDUCIBLE CYTOCHROME-P-450 IN LIVER-MICROSOMES AND RECONSTITUTED MEMBRANES [J].

JOHANSSON, I ;

ELIASSON, E ;

NORSTEN, C ;

INGELMANSUNDBERG, M .

FEBS LETTERS, 1986, 196 (01) :59-64

[14] ETHANOL-INDUCIBLE, FASTING-INDUCIBLE, AND ACETONE-INDUCIBLE CYTOCHROMES-P-450 IN RAT-LIVER - REGULATION AND CHARACTERISTICS OF ENZYMES BELONGING TO THE IIB-GENE AND IIE-GENE SUBFAMILIES [J].

JOHANSSON, I ;

EKSTROM, G ;

SCHOLTE, B ;

PUZYCKI, D ;

JORNVALL, H ;

INGELMANSUNDBERG, M .

BIOCHEMISTRY, 1988, 27 (06) :1925-1934

[15]

JOHANSSON I, 1988, CANCER RES, V48, P5837

[16]

KOOP DR, 1985, J BIOL CHEM, V260, P3607

[17] ROLE OF DIMETHYLNITROSAMINE-DEMETHYLASE IN THE METABOLIC ACTIVATION OF DIMETHYLNITROSAMINE [J].

LAI, DY ;

MYERS, SC ;

WOO, YT ;

GREENE, EJ ;

FRIEDMAN, MA ;

ARGUS, MF ;

ARCOS, JC .

CHEMICO-BIOLOGICAL INTERACTIONS, 1979, 28 (01) :107-126

[18] DIALKYLNITROSAMINE BIOACTIVATION AND CARCINOGENESIS [J].

LAI, DY ;

ARCOS, JC .

LIFE SCIENCES, 1980, 27 (23) :2149-2165

[19]

LEE MJ, 1989, CANCER RES, V49, P1470

[20] ALPHA-NAPHTHYLISOTHIOCYANATE INDUCED ALTERATIONS IN HEPATIC DRUG-METABOLIZING-ENZYMES AND LIVER MORPHOLOGY - IMPLICATIONS CONCERNING ANTI-CARCINOGENESIS [J].

LEONARD, TB ;

POPP, JA ;

GRAICHEN, ME ;

DENT, JG .

CARCINOGENESIS, 1981, 2 (06) :473-482

← 1 2 3 4 5 →