CpG methylation-dependent repression of the human O6-methylguanine-DNA methyltransferase gene linked to chromatin structure alteration.


:The mechanism of inactivation of the O6-methylguanine-DNA methyltransferase (MGMT), responsible for repair of mutagenic and cytotoxic O6-alkylguanine, in Mex- tumor cells, is not completely understood. We have examined the role of CpG methylation in the human MGMT promoter in a luciferase (luc) reporter plasmid and associated alteration in chromatin structure. Methylation of 16% CpG sequences in promoter and flanking sequences in the plasmid with HpaII methylase reduced luciferase activity by 10-12-fold, while methylation of all CpG sites, including those in the luc coding sequence, as well as the promoter sequence blocked expression completely. Repression of luc expression due to partial but not complete CpG methylation could be reversed by histone deacetylase inhibitor trichostatin A (TSA). However, 5-azacytidine, which reverses CpG methylation, but not TSA, could reactivate silent MGMT gene in Mex- HeLa MR cells. Furthermore, chromatin immunoprecipitation (ChIP) assay showed reduced level of acetylation of H4 histone bound to the methylated promoter compared with the non-methylated promoter. These results suggest that complete repression of the MGMT gene in Mex- cells requires methylation of CpG sequences in both promoter and neighboring regions of the gene, resulting in inactive, condensed chromatin state of the gene.






Bhakat KK,Mitra S





Has Abstract


2003-08-01 00:00:00














  • Relationship between the depletion of O6-methylguanine-DNA methyltransferase by O6-methylguanine and the stimulation of DNA synthesis and growth of cultured chick hepatocytes.

    abstract::O6-Methylguanine-DNA methyltransferase (O6-MT) has been described as a DNA repair enzyme that reverses alkylation damage at the O6 position of guanine in DNA. We demonstrate that the concentration of this protein decreases immediately prior to DNA synthesis in cultured chick hepatocytes. If intracellular levels are ex...


    pub_type: 杂志文章


    authors: Dutta-Choudhury TA,Couri D,Stephens RE

    更新日期:1992-01-01 00:00:00

  • Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study.

    abstract::Base excision repair (BER) and nucleotide excision repair (NER) pathways repair damaged DNA, and polymorphisms in these genes might affect breast cancer susceptibility. We evaluated associations between seven single-nucleotide polymorphisms in four DNA repair genes (ERCC4 rs1799801, XPC rs2227998, rs2228001, rs2228000...


    pub_type: 杂志文章


    authors: Roberts MR,Shields PG,Ambrosone CB,Nie J,Marian C,Krishnan SS,Goerlitz DS,Modali R,Seddon M,Lehman T,Amend KL,Trevisan M,Edge SB,Freudenheim JL

    更新日期:2011-08-01 00:00:00

  • Induction by asbestos fibers of anaphase abnormalities: mechanism for aneuploidy induction and possibly carcinogenesis.

    abstract::Syrian hamster embryo cells were treated with crocidolite asbestos at a dose (1 microgram/cm2) which was shown in previous studies to induce cell transformation and aneuploidy in these cells. Treatment of cells with asbestos induced a greater than 20-fold increase in the incidence of cells in anaphase with abnormaliti...


    pub_type: 杂志文章


    authors: Hesterberg TW,Barrett JC

    更新日期:1985-03-01 00:00:00

  • Characterization and properties of the DNA adducts formed from N-methyl-4-aminoazobenzene in rats during a carcinogenic treatment regimen.

    abstract::Chronic oral administration of the carcinogenic aminoazo dye N-methyl-4-aminoazobenzene (MAB) to rats is known to result in the induction of liver tumors. In order to assess the role of carcinogen-DNA adduct formation in MAB hepatocarcinogenesis, male rats were fed 0.06% [3'-3H]MAB in the diet for 1, 3 or 5 weeks. Gro...


    pub_type: 杂志文章


    authors: Tullis DL,Dooley KL,Miller DW,Baetcke KP,Kadlubar FF

    更新日期:1987-04-01 00:00:00

  • Frequent allelic imbalance on chromosome 6 and 17 correlate with radiation-induced neoplastic transformation of human breast epithelial cells.

    abstract::The development of human breast cancer is a complex multi-step process that depends on various exogenous and endogenous factors that modulate the transformation of normal human breast epithelial cells into neoplastic ones. Using a spontaneously-immortalized human breast epithelial (MCF-10F) cell line, we have shown pr...


    pub_type: 杂志文章


    authors: Roy D,Calaf G,Hei TK

    更新日期:2001-10-01 00:00:00

  • Deletion analysis of human AP-endonuclease: minimum sequence required for the endonuclease activity.

    abstract::AP-endonuclease (APE) plays a central role in the base excision repair process for oxidative and alkylation damage in DNA. The major human APE with 318 amino acid residues possesses transcriptional regulatory activities for which the N-terminal region was found to be essential. Systematic deletion studies of both amin...


    pub_type: 杂志文章


    authors: Izumi T,Mitra S

    更新日期:1998-03-01 00:00:00

  • DNA microfiltration assay: a simple technique for detecting DNA damage in mammalian cells.

    abstract::A simple method for detection of DNA single-strand breaks (DNA-SSB) in cultured cells is described, based on filtration of alkaline-lysed cells through microfilters. After exposure to potentially DNA damaging agents, the cells are transferred to 0.8 micron cellulose acetate filters mounted in microfilter devices where...


    pub_type: 杂志文章


    authors: Leanderson P,Wennerberg K,Tagesson C

    更新日期:1994-01-01 00:00:00

  • Carbamoylation reactions of N-methyl-N'-aryl-N-nitrosoureas and corresponding phenyl isocyanates to 5'-amino-5'-deoxythymidine: importance of carbamoylation in mouse skin carcinogenic processes.

    abstract::Carbamoylation reactions of N-methyl-N'-aryl-N-nitrosoureas (I-X: X = -OCH3, -CH3, -H, -Cl, and -COCH3) and of their corresponding phenyl isocyanates (II-X: X = -OCH3, -CH3, -H, -Cl and -COCH3) to the amino group of 5'-amino-5'-deoxythymidine have been kinetically studied in a PBS. The pseudo-first-order rate constant...


    pub_type: 杂志文章


    authors: Yano K

    更新日期:1992-04-01 00:00:00

  • Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1 driven breast cancer.

    abstract::The cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) (p27) is a marker of prognosis in many cancers, including breast cancer. Low p27 expression correlates with poor prognosis, especially in hormone receptor positive breast tumors. This association suggests a role for p27 in hormone-dependent cancer. We used the Wnt-...


    pub_type: 杂志文章


    authors: Glover CE,Gurley KE,Kim KH,Storer B,Fero ML,Kemp CJ

    更新日期:2009-06-01 00:00:00

  • In vivo effects of ascorbate and glutathione on the uptake of chromium, formation of chromium(V), chromium-DNA binding and 8-hydroxy-2'-deoxyguanosine in liver and kidney of osteogenic disorder shionogi rats following treatment with chromium(VI).

    abstract::Several previous in vitro studies have indicated that ascorbate and glutathione are the major reductants of Cr(VI) in cells. In order to evaluate the in vivo effects of ascorbate and glutathione on Cr(VI)-induced carcinogenesis, Cr uptake and the formation of Cr(V), Cr-DNA adducts and 8-hydroxy-2'-deoxyguanosine (8-OH...


    pub_type: 杂志文章


    authors: Yuann JM,Liu KJ,Hamilton JW,Wetterhahn KE

    更新日期:1999-07-01 00:00:00

  • Expression of CYP1B1 but not CYP1A1 by primary cultured human mammary stromal fibroblasts constitutively and in response to dioxin exposure: role of the Ah receptor.

    abstract::The expression of CYP1B1 in human mammary fibroblasts (HMFs) was characterized as a potential modulator of their individual function as well as effects on adjacent mammary epithelia. We have used these characteristics to explore the diversity of fibroblast cells isolated from reduction mammoplasty patients and from di...


    pub_type: 杂志文章


    authors: Eltom SE,Larsen MC,Jefcoate CR

    更新日期:1998-08-01 00:00:00

  • Correlation between clastogenicity and promotion activity in liver carcinogenesis by N-hydroxy-2-acetylaminofluorene, N-hydroxy-4'-fluoro-4-acetylaminobiphenyl and N-hydroxy-4-acetylaminobiphenyl.

    abstract::N-Hydroxy-2-acetylaminofluorene (N-OH-AAF), N-hydroxy-4'-fluoro-4-acetylaminobiphenyl (N-OH-FAABP) and N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) were compared for their initiation and promotion activity in the rat liver using a modified Solt-Farber system. N-OH-AAF, N-OH-FAABP and N-OH-AABP showed comparable initiat...


    pub_type: 杂志文章


    authors: van de Poll ML,van der Hulst DA,Tates AD,Meerman JH

    更新日期:1990-02-01 00:00:00

  • Peroxisome proliferator-activated receptor (PPAR) gamma gene polymorphisms and colorectal cancer risk among Chinese in Singapore.

    abstract::Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-activated nuclear receptor that plays a key role in adipogenesis and adipocyte gene expression, and has recently been linked with possible antineoplastic effects in colonic carcinogenesis. PPARgamma2 and gamma3 are two transcripts arising from the PPA...


    pub_type: 杂志文章


    authors: Koh WP,Yuan JM,Van Den Berg D,Ingles SA,Yu MC

    更新日期:2006-09-01 00:00:00

  • Pretreatment of human colon tumor cells with DNA methylating agents inhibits their ability to repair chloroethyl monoadducts.

    abstract::We have recently shown that a variety of human tumor cell lines are capable of preventing chloroethylnitrosourea (CNU)-induced DNA crosslinks, presumably by removing guanine O6-chloroethyl DNA monoadducts before crosslinks can form. Those cells capable of preventing crosslinking were of the Mer+ (Methylation repair) p...


    pub_type: 杂志文章


    authors: Zlotogorski C,Erickson LC

    更新日期:1984-01-01 00:00:00

  • Synthesis of nitric oxide and nitrosamine by immortalized woodchuck hepatocytes.

    abstract::Woodchuck (Marmota monax) hepatic cells, which were immortalized by the simian virus 40 large T antigen (SV40 Tag) produced nitric oxide (NO; measured as nitrite) in vitro from L-arginine (L-Arg) after lipopolysaccharide (LPS) treatment. NO synthesis was related to L-Arg and LPS concentration and plateaued at 1.0 mM L...


    pub_type: 杂志文章


    authors: Liu RH,Jacob JR,Hotchkiss JH,Tennant BC

    更新日期:1993-08-01 00:00:00

  • Differential repetitive DNA methylation in multiple myeloma molecular subgroups.

    abstract::Multiple myeloma (MM) is characterized by a wide spectrum of genetic changes. Global hypomethylation of repetitive genomic sequences such as long interspersed nuclear element 1 (LINE-1), Alu and satellite alpha (SAT-alpha) sequences has been associated with chromosomal instability in cancer. Methylation status of repe...


    pub_type: 杂志文章


    authors: Bollati V,Fabris S,Pegoraro V,Ronchetti D,Mosca L,Deliliers GL,Motta V,Bertazzi PA,Baccarelli A,Neri A

    更新日期:2009-08-01 00:00:00

  • Protective effects of pregnancy and lactation against N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats.

    abstract::The role of parity before and after N-methyl-N-nitrosourea (MNU) treatment in protection against mammary carcinogenesis was investigated. The effect of lactation on reduction in the incidence of mammary carcinoma was also examined. Parous rats were compared with respective age-matched virgins (AMVs). Pregnancy and lac...


    pub_type: 杂志文章


    authors: Yang J,Yoshizawa K,Nandi S,Tsubura A

    更新日期:1999-04-01 00:00:00

  • Reactions of methylnitrosourea, epichlorohydrin, styrene oxide and acetoxyacetylaminofluorene with polyamino acids.

    abstract::Radioactive methylnitrosourea, epichlorohydrin, styrene oxide, and N-acetoxy-2-acetylaminofluorene were reacted with 14 different polyamino acids in vitro, to determine the relative reactivity of the functional groups in amino acids. All the carcinogens reacted preferentially with polycysteine and much less with polyh...


    pub_type: 杂志文章


    authors: Hemminki K

    更新日期:1983-01-01 00:00:00

  • Differential effects of resveratrol on androgen-responsive LNCaP human prostate cancer cells in vitro and in vivo.

    abstract::Resveratrol is a phytochemical that has been under consideration for use as a prostate cancer chemopreventive agent. However, the efficacy, as well as the mechanisms of action of resveratrol on prostate cancer prevention, remains largely unknown. This study seeks to address these questions and examine the cancer preve...


    pub_type: 杂志文章


    authors: Wang TT,Hudson TS,Wang TC,Remsberg CM,Davies NM,Takahashi Y,Kim YS,Seifried H,Vinyard BT,Perkins SN,Hursting SD

    更新日期:2008-10-01 00:00:00

  • Indole-3-carbinol in the maternal diet provides chemoprotection for the fetus against transplacental carcinogenesis by the polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene.

    abstract::The fetus and neonate are sensitive targets for chemically induced carcinogenesis. Few studies have examined the risk/benefit of chemoprotective phytochemicals, given in the maternal diet, against transplacental carcinogenesis. In this study, B6129 SF1/J (AHR(b-1/d)) and 129Sv/ImJ (AHR(d/d)) mice were cross-bred. The ...


    pub_type: 杂志文章


    authors: Yu Z,Mahadevan B,Löhr CV,Fischer KA,Louderback MA,Krueger SK,Pereira CB,Albershardt DJ,Baird WM,Bailey GS,Williams DE

    更新日期:2006-10-01 00:00:00

  • The suppression of aberrant crypt multiplicity in colonic tissue of 1,2-dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes.

    abstract::Colorectal cancer is the second leading cause of cancer deaths worldwide with diet playing a prominent role in disease initiation and progression. Flavonoids are secondary plant compounds that are suggested as protective ingredients of a diet rich in fruits and vegetables. We here tested whether flavone, a flavonoid t...


    pub_type: 杂志文章


    authors: Winkelmann I,Diehl D,Oesterle D,Daniel H,Wenzel U

    更新日期:2007-07-01 00:00:00

  • Role of the beta isoform of 14-3-3 proteins in cellular proliferation and oncogenic transformation.

    abstract::The 14-3-3 proteins are associated with proto-oncogene and oncogene products. Here, we generated NIH 3T3 cells overexpressing the beta isoform of the 14-3-3 proteins (14-3-3 beta) to examine the function of this isoform in cellular proliferation and oncogenic transformation. Overexpression of 14-3-3 beta in NIH 3T3 ce...


    pub_type: 杂志文章


    authors: Takihara Y,Matsuda Y,Hara J

    更新日期:2000-11-01 00:00:00

  • Enhanced growth of colorectal aberrant crypt foci in fasted/refed rats involves changes in TGFbeta1 and p21CIP expressions.

    abstract::We previously demonstrated that fasting/refeeding enhances the initiation phase of liver and colorectal carcinogenesis in rats. The present study was undertaken to establish whether cycles of fasting/refeeding carried out during the promotion phase of carcinogenesis may also affect the formation of aberrant crypt foci...


    pub_type: 杂志文章


    authors: Caderni G,Perrelli MG,Cecchini F,Tessitore L

    更新日期:2002-02-01 00:00:00

  • Risk of genome-wide association study-identified genetic variants for non-Hodgkin lymphoma in a Chinese population.

    abstract::Recent genome-wide association studies have identified 15 single nucleotide polymorphisms (SNPs) associated with non-Hodgkin lymphoma (NHL) and its subtypes. Because the incidence and subtype portion of NHL between the Chinese population and Caucasian populations are substantially different, we assessed the associatio...


    pub_type: 杂志文章


    authors: Qiao Y,Zhou Y,Wu C,Zhai K,Han X,Chen J,Tian X,Chang J,Lu Z,Zhang B,Yu D,Yao J,Shi Y,Tan W,Lin D

    更新日期:2013-07-01 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

  • Genetic associations with sporadic neuroendocrine tumor risk.

    abstract::Genetic risk factors for sporadic neuroendocrine tumors (NET) are poorly understood. We tested risk associations in patients with sporadic NET and non-cancer controls, using a custom array containing 1536 single-nucleotide polymorphisms (SNPs) in 355 candidate genes. We identified 18 SNPs associated with NET risk at a...


    pub_type: 杂志文章


    authors: Ter-Minassian M,Wang Z,Asomaning K,Wu MC,Liu CY,Paulus JK,Liu G,Bradbury PA,Zhai R,Su L,Frauenhoffer CS,Hooshmand SM,De Vivo I,Lin X,Christiani DC,Kulke MH

    更新日期:2011-08-01 00:00:00

  • Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer.

    abstract::Human papillomavirus (HPV) type 16 infection is an etiologic factor in a subset of head and neck squamous cell carcinomas (HNSCC). It is unknown if host genetic susceptibility modifies the HPV16-HNSCC association. DNA samples collected as part of a Boston area case-control study of HNSCC were genotyped for single-nucl...


    pub_type: 杂志文章


    authors: Chen AA,Marsit CJ,Christensen BC,Houseman EA,McClean MD,Smith JF,Bryan JT,Posner MR,Nelson HH,Kelsey KT

    更新日期:2009-06-01 00:00:00

  • Impairing squamous differentiation by Klf4 deletion is sufficient to initiate tongue carcinoma development upon K-Ras activation in mice.

    abstract::Oral squamous cell carcinoma (SCC) is among the most prevalent cancers in the world and is characterized by high morbidity and few therapeutic options. Like most cancers, oral SCC arises from a multistep process involving alterations of genes responsible for balancing proliferation and differentiation. Among these, Kr...


    pub_type: 杂志文章


    authors: Abrigo M,Alvarez R,Paparella ML,Calb DE,Bal de Kier Joffe E,Gutkind JS,Raimondi AR

    更新日期:2014-03-01 00:00:00

  • Metabolism of aflatoxin B1 in the bovine olfactory mucosa.

    abstract::Carcinomas of the ethmoidal region of the nose are observed relatively frequently in cattle in several countries in tropical and subtropical latitudes. Viruses have been implicated as causative agents, but it has been observed that affected animals sometimes suffer from aflatoxicosis, and a role of aflatoxin B1 (AFB1)...


    pub_type: 杂志文章


    authors: Larsson P,Pettersson H,Tjälve H

    更新日期:1989-06-01 00:00:00

  • Evidence that N-acetoxy-N-acetyl-2-aminofluorene crosslinks DNA to protein by a free radical mechanism.

    abstract::A method was devised to quantitate N-acetoxy-N-acetyl-2-aminofluorene (N-AcO-AAF) induced crosslinking of the ionic complex between [methyl-3H]thymidine labeled pBR322 DNA and lysozyme. This involved chromatography of the modified complex on Sephadex CM 25 with a high salt buffer that dissociated the non-covalently bo...


    pub_type: 杂志文章


    authors: Rayshell M,Ross J,Werbin H

    更新日期:1983-01-01 00:00:00