CYP2E1-mediated mechanism of anti-genotoxicity of the broccoli constituent sulforaphane.


:The broccoli constituent sulforaphane (1-isothiocyanate-4-methylsulfinylbutane) has previously been shown to protect rats against 9,10-dimethyl-1,2-benz[a]anthracene tumorigenesis, thought to be due, at least in part, to induction of phase II detoxification. We investigated the ability of sulforaphane to also inhibit the phase I enzyme cytochrome P450 isoenzyme 2E1 (CYP2E1), which is responsible for activation of several carcinogens, including dialkylnitrosamines. Using the p-nitrophenol hydroxylation assay in microsomes from livers of acetone-treated Sprague-Dawley rats, sulforaphane was shown to be a potent competitive inhibitor of CYP2E1 with a Ki of 37.0 +/- 4.5 microM. In view of this result, we studied the capacity of sulforaphane to inhibit the genotoxicity of N-nitrosodimethylamine (NDMA). Sulforaphane at concentrations of > 0.8 microM inhibited the mutagenicity of NDMA (4.4 mg/plate) in Salmonella typhimurium strain TA100 after pre-incubation for 45 min with cytosol extract from livers of Balb/c mice pre-treated with acetone. Unscheduled DNA synthesis induced by NDMA (33.5 microM) in mouse hepatocytes was inhibited in a dose-dependent manner by sulforaphane at 0.064-20 microM. Sulforaphane was unable to inhibit mutagenicity of sodium azide (5 micrograms/plate), a direct acting mutagen, in the Salmonella assay. It was not itself genotoxic in hepatocytes, as measured by unscheduled DNA synthesis, or mutagenic in the strain of Salmonella employed and cytotoxic only at high concentrations (> or = 0.5 mM). These findings suggest that inhibition of CYP2E1 by sulforaphane may offer chemoprotection against carcinogenic substrates of this enzyme.






Barcelo S,Gardiner JM,Gescher A,Chipman JK




Has Abstract


1996-02-01 00:00:00












  • Elevated polyamines lead to selective induction of apoptosis and inhibition of tumorigenesis by (-)-epigallocatechin-3-gallate (EGCG) in ODC/Ras transgenic mice.

    abstract::Tea polyphenolic constituents induce apoptosis in cancer cells but not in normal cells. To study the mechanism of this selective effect, we used the ornithine decarboxylase (ODC)/Ras double transgenic mouse model that develops spontaneous skin tumors due to over-expression of ODC and a v-Ha-ras transgene. Administrati...


    pub_type: 杂志文章


    authors: Paul B,Hayes CS,Kim A,Athar M,Gilmour SK

    更新日期:2005-01-01 00:00:00

  • Comparison of the mutagenic activity of dialkylnitrosamines in animal-mediated and in vitro assays using an Escherichia coli indicator.

    abstract::An intrasanguineous host-mediated assay was used to establish the mutagenic potential of a series of dialkylnitrosamines to E. coli K12/343/113 in the liver and spleen of mice. For calibrating purposes, dose- and time-dependent kinetics of mutation induction by the model compound diethylnitrosamine in this assay was d...


    pub_type: 杂志文章


    authors: Kerklaan P,Mohn G,Bouter S

    更新日期:1981-01-01 00:00:00

  • Prostaglandin H synthase-mediated bioactivation of the amino acid pyrolysate product Trp P-2.

    abstract::We report evidence that the mutagen and carcinogen 3-amino-1-methyl-5H pyrido[4,3b]indole (Trp P-2) is a substrate for co-oxidation by prostaglandin H synthase (PHS) in ram seminal vesicle (RSV) microsomes. Trp P-2 serves as a reducing cofactor for the hydroperoxidase activity of PHS as shown by the concentration-depe...


    pub_type: 杂志文章


    authors: Petry TW,Krauss RS,Eling TE

    更新日期:1986-08-01 00:00:00

  • Meat and cancer: haemoglobin and haemin in a low-calcium diet promote colorectal carcinogenesis at the aberrant crypt stage in rats.

    abstract::High intake of red meat, but not of white meat, is associated with an increased risk of colon cancer. However, red meat does not promote cancer in rodents. Haemin, added to low-calcium diets, increases colonic proliferation, and haemoglobin, added to high-fat diets, increases the colon tumour incidence in rats, an eff...


    pub_type: 杂志文章


    authors: Pierre F,Taché S,Petit CR,Van der Meer R,Corpet DE

    更新日期:2003-10-01 00:00:00

  • Induction of hepatic heme oxygenase-1 and ferritin in rats by cancer chemopreventive dithiolethiones.

    abstract::Treatment of rats with the cancer chemopreventive agent 1,2-dithiole-3-thione (D3T) resulted in a significant increase in hepatic heme oxygenase (HO) activity, which corresponded to increased protein levels of HO-1. Upon further analysis of proteins related to heme metabolism, the level of ferritin, the major iron sto...


    pub_type: 杂志文章


    authors: Primiano T,Kensler TW,Kuppusamy P,Zweier JL,Sutter TR

    更新日期:1996-11-01 00:00:00

  • Polymorphisms in DNA repair genes in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma.

    abstract::To test the hypothesis that aberrations of DNA repair contribute to susceptibility for the progression of gastroesophageal reflux disease (GERD) into Barrett esophagus (BE) and esophageal adenocarcinoma (EADC), we studied the frequency of polymorphisms of selected DNA repair genes in patients with GERD (n = 126), BE (...


    pub_type: 杂志文章


    authors: Casson AG,Zheng Z,Evans SC,Veugelers PJ,Porter GA,Guernsey DL

    更新日期:2005-09-01 00:00:00

  • Absence of mutations in the functional parts of the p120-GAP gene in carcinogen-induced mouse liver tumors.

    abstract::The GTPase activating proteins (GAP) stimulate the intrinsic GTPase activity of ras-p21 thus converting the protein into its inactive form. We have now analyzed carcinogen-induced mouse liver tumors for the possible occurrence of mutational changes in one of the two known GAP genes, namely p120-GAP. RNA from a total o...


    pub_type: 杂志文章


    authors: Müller O,Kress S,Schwarz M

    更新日期:1992-10-01 00:00:00

  • Foreign compound metabolism capacity in man measured from metabolites of dietary caffeine.

    abstract::Caffeine is sequentially metabolized by cytochrome P4501A2 (CYP1A2), N-acetyltransferase (NAT) and/or xanthine oxidase (XO). In the present study the activity of these three enzymes was estimated from ratios of the metabolites formed from dietary caffeine and excreted into the urine collected as spot samples. In the u...


    pub_type: 杂志文章


    authors: Vistisen K,Poulsen HE,Loft S

    更新日期:1992-09-01 00:00:00

  • Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-κB and inhibition of monocyte chemoattractant protein-1 in urethane-induced lung tumor model.

    abstract::To evaluate the significance of C-C chemokine receptor type 5 (CCR5) in lung tumor development, we compared carcinogen-induced tumor growth in CCR5 knockout (CCR5(-/-)) mice and wild-type (CCR5(+/+)) mice. CCR5(-/-) mice showed reduced urethane (1g/kg)-induced tumor incidence when compared with those of CCR5(+/+) mice...


    pub_type: 杂志文章


    authors: Lee NJ,Choi DY,Song JK,Jung YY,Kim DH,Kim TM,Kim DJ,Kwon SM,Kim KB,Choi KE,Moon DC,Kim Y,Han SB,Hong JT

    更新日期:2012-12-01 00:00:00

  • Allyl mercaptan, a garlic-derived organosulfur compound, inhibits histone deacetylase and enhances Sp3 binding on the P21WAF1 promoter.

    abstract::Histone deacetylase (HDAC) inhibitors have the potential to derepress epigenetically silenced genes in cancer cells, leading to cell cycle arrest and apoptosis. In the present study, we screened several garlic-derived small organosulfur compounds for their ability to inhibit HDAC activity in vitro. Among the organosul...


    pub_type: 杂志文章


    authors: Nian H,Delage B,Pinto JT,Dashwood RH

    更新日期:2008-09-01 00:00:00

  • Phenotypic expression of carcinogen-initiated epidermal cells to tumor cells by 12-O-tetradecanoylphorbol-13-acetate in a manner dependent on 3T3 fibroblast-derived humoral factor(s).

    abstract::Primary cultured newborn mouse epidermal cells cultured in the low Ca2+ (0.02 mM) medium showed typical basal cell morphology and proliferated as a monolayer. A stepwise increase in medium Ca2+ concentration induced terminal differentiation of epidermal cells. In the case of epidermal cells obtained from newborn mice ...


    pub_type: 杂志文章


    authors: Wang JC,Yamamoto S,Kato R

    更新日期:1992-08-01 00:00:00

  • P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers.

    abstract::Sequencing of p53 exons 5-8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mu...


    pub_type: 杂志文章


    authors: LaRue H,Allard P,Simoneau M,Normand C,Pfister C,Moore L,Meyer F,Têtu B,Fradet Y

    更新日期:2000-01-01 00:00:00

  • Msh2 deficiency enhances somatic Apc and p53 mutations in Apc+/-Msh2-/- mice.

    abstract::Inactivation of the adenomatous polyposis coli (Apc) gene by loss of the wild-type Apc allele (LOH) is a prerequisite for the development of intestinal adenomas in Msh2 proficient Min (Apc+/-Msh2+/+) mice. In contrast, adenomas from Msh2 deficient Min (Apc+/-Msh2-/-) mice are not usually associated with LOH. Given the...


    pub_type: 杂志文章


    authors: Sohn KJ,Choi M,Song J,Chan S,Medline A,Gallinger S,Kim YI

    更新日期:2003-02-01 00:00:00

  • Metabolic cooperation in SK-HEP-1 human hepatoma cells following treatment with benzodiazepine tranquilizers.

    abstract::The ability of three benzodiazepine tranquilizers, diazepam, oxazepam and chlordiazepoxide chlorhydrate to block metabolic cooperation between human hepatoma cells was analysed using autoradiographical monitoring. Independent tests were performed with compound concentrations varying from 1 to 50 micrograms/ml. The res...


    pub_type: 杂志文章


    authors: Rolin-Limbosch S,Moens W,Szpirer C

    更新日期:1987-07-01 00:00:00

  • In vitro enzymatic recognition of DNA modified by O,O'-diacetyl or O-acetyl derivatives of the carcinogen 4-hydroxyaminoquinoline-1-oxide.

    abstract::Purified DNA was modified in vitro by 3H-labelled O-acetyl or O,O'-diacetyl-4-hydroxyaminoquinoline-1-oxide (Ac4HAQO or di Ac-4HAQO). It was then subjected to the action of the single-stranded DNA specific nuclease S1 and the digested fractions were analysed. For both types of modified DNA, the release of non-modified...


    pub_type: 杂志文章


    authors: Galiègue S,Bailleul B,Loucheux-Lefebvre MH,Laval J

    更新日期:1982-01-01 00:00:00

  • GDP-fucose:GM1 alpha 1----2fucosyltransferase is activated in parenchymal cells of rat liver during early stages of N-2-acetylaminofluorene induced hepatocarcinogenesis.

    abstract::Gangliosides from liver parenchymal and non-parenchymal cells were isolated from Fischer 344 rats that had been fed normal diet or a diet supplemented with 0.03% N-2-acetylaminofluorene (AAF) for 4 weeks. Gangliosides from liver cell fractions were characterized by an induction of both II3NeuAcIV3 alpha GalIV2FucGg4 a...


    pub_type: 杂志文章


    authors: Holmes EH

    更新日期:1990-01-01 00:00:00

  • Alkylation of haemoglobin, plasma proteins and DNA in the mouse by diethylnitrosamine.

    abstract::Covalent binding to haemoglobin, plasma proteins and DNA was determined after intraperitoneal administration of radiolabelled diethylnitrosamine to mice. The level of alkylation of DNA in liver--the main site of activation--was found to be about two orders of magnitude higher than the level of alkylation of haemoglobi...


    pub_type: 杂志文章


    authors: Osterman-Golkar S,Bergmark E

    更新日期:1988-11-01 00:00:00

  • Increased formation of hepatic N2-ethylidene-2'-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol.

    abstract::N2-ethylidene-2'-deoxyguanosine (N2-ethylidene-dG) is a major DNA adduct induced by acetaldehyde. Although it is unstable in the nucleoside form, it is relatively stable when present in DNA. In this study, we analyzed three acetaldehyde-derived DNA adducts, N2-ethylidene-dG, N2-ethyl-2'-deoxyguanosine (N2-Et-dG) and a...


    pub_type: 杂志文章


    authors: Matsuda T,Matsumoto A,Uchida M,Kanaly RA,Misaki K,Shibutani S,Kawamoto T,Kitagawa K,Nakayama KI,Tomokuni K,Ichiba M

    更新日期:2007-11-01 00:00:00

  • Induction of the aromatic hydrocarbon receptor by trans-4-acetylaminostilbene in rat liver. Comparison with other aromatic amines.

    abstract::The effect of the aromatic amines 2-acetylaminofluorene (AAF), 2-acetylaminophenanthrene (AAP) and trans-4-acetylaminostilbene (AAS) on the rat hepatic aromatic hydrocarbon (Ah) receptor level was studied. 3-Methylcholanthrene (MC), as a known receptor ligand, was used as a control. The complete liver carcinogen AAF a...


    pub_type: 杂志文章


    authors: Göttlicher M,Cikryt P

    更新日期:1987-07-01 00:00:00

  • A microRNA-135a/b binding polymorphism in CD133 confers decreased risk and favorable prognosis of lung cancer in Chinese by reducing CD133 expression.

    abstract::CD133 is a pivotal marker of cancer stem cells (CSCs), which is involved in tumorigenesis and cancer progression. Recent studies have identified CD133 to be a prognostic factor for cancer rested with its expression and genetic variants. Here, we hypothesized that the single nuclear polymorphisms (SNPs) in CD133 may be...


    pub_type: 杂志文章


    authors: Cheng M,Yang L,Yang R,Yang X,Deng J,Yu B,Huang D,Zhang S,Wang H,Qiu F,Zhou Y,Lu J

    更新日期:2013-10-01 00:00:00

  • PDGF AA as mediator in nicotine-dependent carcinogenesis.

    abstract::Effect of nicotine on PDGF AA and PDGF BB interaction with cervical cancer SiHa cells was tested. [125I]PDGF AA was internalized by cells and accumulated in the cytoplasm and nucleus (chromatin). In the absence of nicotine, maximal accumulation of [125I]PDGF AA inside the cells occurred after 1 day of incubation, whic...


    pub_type: 杂志文章


    authors: Rakowicz-Szulczynska EM,McIntosh DG,Perry M,Smith ML

    更新日期:1996-09-01 00:00:00

  • Microsome-mediated alkylation of rat liver initiator tRNA by 3,3-dimethyl-1-phenyltriazene and its ring-chlorinated derivatives.

    abstract::3,3-[3H]Dimethyl-1-phenyltriazene, 1-(4-chlorophenyl)-3,3-[3H]dimethyltriazene and 3,3-[3H]dimethyl-1-(2,4,6-trichlorophenyl)-triazene methylate initiator tRNA in vitro only after pre-incubation with microsomal enzymes and NADPH. The finding confirms that procarcinogenic dialkyl aryltriazenes must be enzymatically con...


    pub_type: 杂志文章


    authors: Hradec J,Kolar GF

    更新日期:1985-07-01 00:00:00

  • Sulindac reversal of 15-PGDH-mediated resistance to colon tumor chemoprevention with NSAIDs.

    abstract::Non-steroidal anti-inflammatory drugs prevent colorectal cancer by inhibiting cyclooxygenase (COX) enzymes that synthesize tumor-promoting prostaglandins. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a tumor suppressor that degrades tumor-promoting prostaglandins. Murine knockout of 15-PGDH increases susceptibil...


    pub_type: 杂志文章


    authors: Fink SP,Dawson DM,Zhang Y,Kresak A,Lawrence EG,Yang P,Chen Y,Barnholtz-Sloan JS,Willis JE,Kopelovich L,Markowitz SD

    更新日期:2015-02-01 00:00:00

  • Effect of diet and route of administration on the DNA binding of aflatoxin B1 in the rat.

    abstract::The effects of dietary Brussels sprouts and indole-3-carbinol (I3C) on xenobiotic-metabolizing enzyme activities and hepatic aflatoxin B1 (AFB1)-DNA binding were determined in rats. Animals were dosed intraperitoneally (i.p.) or intragastrically (i.g.) with [3H]AFB1 and killed 2 (i.p.) or 3 (i.g.) h later. Brussels sp...


    pub_type: 杂志文章


    authors: Salbe AD,Bjeldanes LF

    更新日期:1989-04-01 00:00:00

  • The Escherichia coli MutS DNA mismatch binding protein specifically binds O(6)-methylguanine DNA lesions.

    abstract::DNA mismatch repair defects in certain cell types confer resistance to the cytotoxic effects of alkylating agents, suggesting that a normally functioning DNA mismatch repair pathway can actually mediate alkylation-induced cell death. In eukaryotic cells this phenomenon is only observed in cells lacking adequate DNA me...


    pub_type: 杂志文章


    authors: Rasmussen LJ,Samson L

    更新日期:1996-09-01 00:00:00

  • Docosahexaenoic acid alters epidermal growth factor receptor-related signaling by disrupting its lipid raft association.

    abstract::Docosahexaenoic acid (DHA), a 22:6 n-3 polyunsaturated fatty acid, is the longest and most highly unsaturated fatty acid found in most membranes and has been shown to inhibit cancer cell growth in part by modifying cell signaling. In the current study, alterations to epidermal growth factor receptor (EGFR) signaling u...


    pub_type: 杂志文章


    authors: Rogers KR,Kikawa KD,Mouradian M,Hernandez K,McKinnon KM,Ahwah SM,Pardini RS

    更新日期:2010-09-01 00:00:00

  • Role of the maternal environment in determining susceptibility to transplacentally induced chemical carcinogenesis in mouse fetuses.

    abstract::Treatment of pregnant mice with 3-methylcholanthrene (MC) causes lung and liver tumors in the offspring, the incidences of which are greatly influenced by the Ah locus regulated induction phenotype for aryl hydrocarbon hydroxylase activity (AHH) in both the mother and fetuses. In order to examine the biochemical and m...


    pub_type: 杂志文章


    authors: Miller MS,Jones AB,Chauhan DP,Anderson LM

    更新日期:1990-11-01 00:00:00

  • Mammary carcinogenesis in transgenic mice expressing a dominant-negative mutant of DNA polymerase beta in their mammary glands.

    abstract::DNA polymerase beta (polbeta) is a major contributor to mammalian DNA damage repair through its gap-filling DNA synthesis and 5'-deoxyribose phosphate lyase activities. In this way, polbeta plays pivotal roles in the repair of oxidative DNA damage, replication, embryonic survival, neuronal development, meiosis, apopto...


    pub_type: 杂志文章


    authors: Wang L,Bhattacharyya N,Rabi T,Wang L,Banerjee S

    更新日期:2007-06-01 00:00:00

  • Interrelationships among angiogenesis, proliferation, and apoptosis in the tumor microenvironment during N-methyl-N-nitrosourea androgen-induced prostate carcinogenesis in rats.

    abstract::Proliferation, apoptosis and angiogenesis are critical biologic processes altered during carcinogenesis. Surrogate biomarkers of these processes represent potential intermediate endpoints for short-term intervention studies with preventive and therapeutic agents. We examined the interrelationships among these processe...


    pub_type: 杂志文章


    authors: Liao Z,Boileau TW,Erdman JW Jr,Clinton SK

    更新日期:2002-10-01 00:00:00

  • Regulation of mdr1b gene expression in Fischer, Wistar and Sprague-Dawley rats in vivo and in vitro.

    abstract::Administration of 2-acetylaminofluorene (2-AAF) to rats increased mdr1b expression in Fischer, Wistar and Sprague-Dawley rat livers; however, the response was much smaller in Sprague-Dawley livers. To investigate the basis of this difference we further examined the regulation of the mdr1b gene in hepatocytes isolated ...


    pub_type: 杂志文章


    authors: Hill BA,Brown PC,Preisegger KH,Silverman JA

    更新日期:1996-03-01 00:00:00