The R438W polymorphism of human DNA polymerase lambda triggers cellular sensitivity to camptothecin by compromising the homologous recombination repair pathway.

Abstract:

:The human DNA polymerase lambda (Polλ) is a DNA repair polymerase, which is believed not only to play a role in base excision repair but also to contribute to DNA double-strand break repair by non-homologous end joining. We described here that cellular expression of the recently described natural polymorphic variant of Polλ, Polλ(R438W), affects the homologous recombination (HR) pathway and sister chromatid exchange (SCE) events. We show that the HR defect provoked by this polymorphism enhances cellular sensitivity to the anticancer agent camptothecin (CPT), most of whose DNA damage is repaired by HR. All these effects were dependent on the DNA polymerase activity of Polλ(R438W) as the expression of a catalytically inactive Polλ(R438W) did not affect either the HR and SCE frequencies or the cellular sensitivity to CPT. These results suggest that sensitivity to CPT could result from cancer-related mutation in specialized DNA repair polymerases.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Capp JP,Boudsocq F,Bergoglio V,Trouche D,Cazaux C,Blanco L,Hoffmann JS,Canitrot Y

doi

10.1093/carcin/bgq166

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

1742-7

issue

10

eissn

0143-3334

issn

1460-2180

pii

bgq166

journal_volume

31

pub_type

杂志文章
  • TIPE1 promotes cervical cancer progression by repression of p53 acetylation and is associated with poor cervical cancer outcome.

    abstract::Previous studies have shown that TIPE1 inhibits tumor proliferation and metastasis in certain cancers; however, increased expression of TIPE1 is observed in cervical cancer cell lines and tissues, indicating it might exert a distinctive role in cervical cancer. Cell and xenograft tumorigenicity assays showed that TIPE...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgy163

    authors: Zhao P,Pang X,Jiang J,Wang L,Zhu X,Yin Y,Zhai Q,Xiang X,Feng F,Xu W

    更新日期:2019-06-10 00:00:00

  • Intestinal metabolism of nitrosamines. 1. Transport and metabolism of six nitrosamines in isolated perfused rat small intestinal segments.

    abstract::Possible relationships between structure and metabolism of nitrosamines have been investigated in the rat small intestine. Isolated segments of jejunum and ileum were perfused from the luminal side for 2 h with a Tyrode solution containing one of four symmetrical dialkylnitrosamines with 2-5 carbon atoms per side chai...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/7.7.1207

    authors: Richter E,Richter-Cooberg U,Feng X,Schulze J,Wiessler M

    更新日期:1986-07-01 00:00:00

  • Extra-virgin olive oil contains a metabolo-epigenetic inhibitor of cancer stem cells.

    abstract::Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of ext...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgy023

    authors: Corominas-Faja B,Cuyàs E,Lozano-Sánchez J,Cufí S,Verdura S,Fernández-Arroyo S,Borrás-Linares I,Martin-Castillo B,Martin ÁG,Lupu R,Nonell-Canals A,Sanchez-Martinez M,Micol V,Joven J,Segura-Carretero A,Menendez JA

    更新日期:2018-04-05 00:00:00

  • Association of viral oncogene-induced changes in gap junctional intercellular communication and morphological transformation in BALB/c3T3 cells.

    abstract::In order to study the relationship between altered gap junctional intercellular communication (GJIC) and induction of cell transformation by oncogenes, we transfected six viral oncogenes into BALB/c3T3 A31-1-1 cells. BALB/c3T3 cells with v-src, v-ras or polyoma middle T (PyMT) genes grew in soft agar and formed distin...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.3.435

    authors: Katoh F,Klein JL,Bignami M,Yamasaki H

    更新日期:1993-03-01 00:00:00

  • Aromatic DNA adducts, micronuclei and genetic polymorphism for CYP1A1 and GST1 in chimney sweeps.

    abstract::Aromatic DNA adducts in total white blood cells, cytochrome P450 (CYP) class 1A1 and glutathione transferase (GST1) class mu genotypes and micronuclei in T- and B-lymphocytes were studied in 69 full-time chimney sweeps and 35 controls, all male subjects. The sweeps had a higher (22%) but statistically non-significant ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.7.1347

    authors: Ichiba M,Hagmar L,Rannug A,Högstedt B,Alexandrie AK,Carstensen U,Hemminki K

    更新日期:1994-07-01 00:00:00

  • Initiating activity of 3-tert-butyl-4-hydroxyanisole (3-BHA) and its metabolites in two-stage transformation of BALB/3T3 cells.

    abstract::3-tert-Butyl-4-hydroxyanisole (3-BHA) and its metabolites, tert-butyl-1,4-benzoquinone (BQ) and 3-tert-butyl-5-methoxy-1,2-benzoquinone (BHAoQ), were tested for initiating activity in a two-stage transformation assay using BALB/3T3 cells. Cells were treated first with a test chemical and then with the tumor promoter 1...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.11.1985

    authors: Sakai A,Miyata N,Takahashi A

    更新日期:1990-11-01 00:00:00

  • SCYL1 binding protein 1 promotes the ubiquitin-dependent degradation of Pirh2 and has tumor-suppressive function in the development of hepatocellular carcinoma.

    abstract::Pirh2 is a Ring-H2 domain containing E3 ubiquitin ligase that targets several important tumor suppressor genes for proteasomal degradation. Overexpression of Pirh2 is frequently detected in many clinical tumor tissues including hepatocellular carcinoma (HCC). However, the molecular mechanism of Pirh2 activation in tum...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs162

    authors: Hu L,Liu M,Chen L,Chan TH,Wang J,Huo KK,Zheng BJ,Xie D,Guan XY

    更新日期:2012-08-01 00:00:00

  • Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China.

    abstract::Epidemiological evidence has suggested that consumption of a diet rich in cruciferous vegetables reduces the risk of several types of cancers and chronic degenerative diseases. In particular, broccoli sprouts are a convenient and rich source of the glucosinolate, glucoraphanin, which can release the chemopreventive ag...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/carcin/bgr229

    authors: Kensler TW,Ng D,Carmella SG,Chen M,Jacobson LP,Muñoz A,Egner PA,Chen JG,Qian GS,Chen TY,Fahey JW,Talalay P,Groopman JD,Yuan JM,Hecht SS

    更新日期:2012-01-01 00:00:00

  • Butyrylated starch protects colonocyte DNA against dietary protein-induced damage in rats.

    abstract::Dietary resistant starch (RS), as a high amylose maize starch (HAMS), prevents dietary protein-induced colonocyte genetic damage in rats, possibly through the short-chain fatty acid (SCFA) butyrate produced by large bowel bacterial RS fermentation. Increasing butyrate availability may improve colonic health and dietar...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn173

    authors: Bajka BH,Clarke JM,Cobiac L,Topping DL

    更新日期:2008-11-01 00:00:00

  • The use of micro RNA in the early detection of cervical intraepithelial neoplasia.

    abstract::An important issue in current oncological research is prevention as well as early detection of cancer. This includes also the difficulty to predict the progression of early or pre-cancerous lesions to invasive cancer. In this context, the characterization and categorization of pre-neoplastic lesions of squamous cell c...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgaa046

    authors: Wittenborn J,Weikert L,Hangarter B,Stickeler E,Maurer J

    更新日期:2020-12-31 00:00:00

  • A 7-hydroxymethyl sulphate ester as an active metabolite of the carcinogen, 7-hydroxymethylbenz[a]anthracene.

    abstract::7-Hydroxymethylbenz[a]anthracene (7-HBA) showed potent mutagenicity towards Salmonella typhimurium TA 98 in the presence of untreated rat liver cytosol fortified with the PAPS-generating system, sodium sulphate and ATP. No mutagenic activity was observed either when the cytosol was boiled or when sodium sulphate or AT...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/7.2.207

    authors: Watabe T,Hakamata Y,Hiratsuka A,Ogura K

    更新日期:1986-02-01 00:00:00

  • Estrogen-responsive RING finger mRNA induction in gastrointestinal carcinoma cells following bile acid treatment.

    abstract::The underlying molecular mechanisms of the tumor-promoting activity of bile acids such as chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) and the protective effect of ursodeoxycholic acid (UDCA) remain largely unclear. Using RNA arbitrarily primed PCR (RAP-PCR) for differential display, we identified, cloned a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.11.1901

    authors: Jung B,Vogt T,Mathieu-Daudé F,Welsh J,McClelland M,Trenkle T,Weitzel C,Kullmann F

    更新日期:1998-11-01 00:00:00

  • O6-ethylguanine and O6-benzylguanine incorporated site-specifically in codon 12 of the rat H-ras gene induce semi-targeted as well as targeted mutations in Rat4 cells.

    abstract::To examine the miscoding properties of modified guanine residues bearing increasingly bulky O6-substituents, Rat4 cells, grown in the presence of O6-benzylguanine to deplete the DNA repair protein O6-alkylguanine-DNA alkyltransferase, were transfected with plasmids carrying H-ras genes in which O6-methyl, O6-ethyl- an...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.4.849

    authors: Bishop RE,Pauly GT,Moschel RC

    更新日期:1996-04-01 00:00:00

  • 32P-post-labelling analysis of DNA adducts formed by food-derived heterocyclic amines: evidence for incomplete hydrolysis and a procedure for adduct pattern simplification.

    abstract::Food-derived aminoimidazoazarenes have been shown to be mutagenic and carcinogenic and to form covalent DNA adducts. 32P-Post-labelling analysis of DNA modified with these heterocyclic amines (HA), including 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.5.877

    authors: Pfau W,Brockstedt U,Söhren KD,Marquardt H

    更新日期:1994-05-01 00:00:00

  • The effects of alternating dietary restriction and ad libitum feeding of mice on the development of diethylnitrosamine-induced liver tumours and its correlation to insulinaemia.

    abstract::The effects of alternating ad libitum feeding and 30% restriction of the dietary intake on the development of diethylnitrosamine (DEN)-induced hepatic neoplasia were investigated. Dietary restriction retarded the growth of glucose-6-phosphatase-deficient (G6Pd) preneoplastic foci and subsequently that of hepatocellula...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.2.311

    authors: Lagopoulos L,Sunahara GI,Würzner H,Dombrowsky I,Stalder R

    更新日期:1991-02-01 00:00:00

  • Identification and mutagenicity of metabolites of aristolochic acid formed by rat liver.

    abstract::The rat liver 9000 g supernatant mediated metabolism of the carcinogenic aristolochic acid, which consists of aristolochic acid I (AAI) and aristolochic acid II (AAII), was investigated. Under anaerobic conditions the major metabolites were the corresponding aristolactams for both AAI and AAII. In contrast under aerob...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/7.1.59

    authors: Schmeiser HH,Pool BL,Wiessler M

    更新日期:1986-01-01 00:00:00

  • Diacylglycerol is an effector of the clonal expansion of cells containing activated Ha-ras genes.

    abstract::Diacylglycerols (DAG) are lipid second messengers which are generated during phospholipase-catalyzed hydrolysis of phospholipids. The model DAG, sn-1,2-didecanoylglycerol (DIC10), is an effective topical tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. We now report that 11/12 of DMBA-init...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.12.2645

    authors: Mills KJ,Reynolds SH,Smart RC

    更新日期:1993-12-01 00:00:00

  • Pre-natal factors in the origin of germ cell tumours of childhood.

    abstract::The Manchester (England) Children's Tumour Registry is population-based with a high level of ascertainment. Pathologic review ensured diagnostic accuracy. Routine monitoring of annual incidence revealed a significant increase in germ cell tumours from approximately 1 per million person years to approximately 4. Analys...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.1.75

    authors: Birch JM,Marsden HB,Swindell R

    更新日期:1982-01-01 00:00:00

  • Sequential and morphological analyses of aberrant crypt foci formation in mice of differing susceptibility to azoxymethane-induced colon carcinogenesis.

    abstract::Aberrant crypt foci (ACF), putative preneoplastic lesions, are early morphological changes induced by the colon carcinogen azoxymethane (AOM). Although inbred mice differ markedly in their susceptibility to AOM carcinogenesis, we have previously shown that ACF develop in both resistant and sensitive mouse strains afte...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:

    authors: Papanikolaou A,Wang QS,Papanikolaou D,Whiteley HE,Rosenberg DW

    更新日期:2000-08-01 00:00:00

  • The chemopreventive flavonoid apigenin induces G2/M arrest in keratinocytes.

    abstract::Apigenin is a plant flavonoid which has been shown to significantly inhibit UV-induced mouse skin tumorigenesis when applied topically, and may represent an alternative sunscreen agent in humans. We have investigated the molecular mechanism(s) by which apigenin inhibits skin tumorigenesis. Initial studies examined the...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.11.2367

    authors: Lepley DM,Li B,Birt DF,Pelling JC

    更新日期:1996-11-01 00:00:00

  • Time-related induction of DNA repair synthesis in rat hepatocytes following in vivo treatment with cyproterone acetate.

    abstract::Cyproterone acetate (CPA), a synthetic steroid hormone widely used as a human pharmaceutical, has recently been shown to induce unscheduled DNA synthesis (UDS) in vitro in primary cultures of rat and human hepatocytes. In the present study CPA was evaluated for its ability to initiate UDS in the liver of female rats i...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.10.2271

    authors: Kasper P,Mueller L

    更新日期:1996-10-01 00:00:00

  • The redox protein thioredoxin-1 regulates the constitutive and inducible expression of the estrogen metabolizing cytochromes P450 1B1 and 1A1 in MCF-7 human breast cancer cells.

    abstract::The oxidative metabolites of estrogen have been proposed to play an important role in the development of some human cancers. The two major pathways of estrogen metabolism, to the carcinogenic 4-hydroxyestradiol (4-OHE2) and to the non-carcinogenic 2-hydroxyestradiol (2-OHE2), are mediated by cytochromes P450 CYP1B1 an...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.10.1625

    authors: Husbeck B,Powis G

    更新日期:2002-10-01 00:00:00

  • Integrin-linked kinase regulates osteopontin-dependent MMP-2 and uPA expression to convey metastatic function in murine mammary epithelial cancer cells.

    abstract::Metastasis-supporting physiological alterations are regulated by cell signaling molecules, which target signal transduction pathways and gene expression. Osteopontin (OPN) overexpression may represent a key molecular event in cancer metastasis. In this study, using metastatic 4T1 and non-metastatic 4T07 murine mammary...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi352

    authors: Mi Z,Guo H,Wai PY,Gao C,Kuo PC

    更新日期:2006-06-01 00:00:00

  • Exposure of Fischer 344 rats to a weak power frequency magnetic field facilitates mammary tumorigenesis in the DMBA model of breast cancer.

    abstract::The possibility that long-term exposure to relatively weak power frequency magnetic fields (MFs) emanating from the generation, transmission and use of electricity could increase the risk of breast cancer is a matter of ongoing debate. Laboratory studies using well-defined exposure conditions are useful to examine whe...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgm217

    authors: Fedrowitz M,Löscher W

    更新日期:2008-01-01 00:00:00

  • Increased susceptibility to oxidative DNA damage in regenerating liver.

    abstract::Spontaneous and hepatocarcinogen (2-nitropropane, 2-NP)-induced levels of 8-hydroxy-2'-deoxyguanosine (oh8dG) in the nuclear DNA of regenerating liver [24, 48, 72 h and 7 days after partial hepatectomy (PH)] of male Sprague-Dawley rats were analysed for the verification of a hypothesis that the high susceptibility of ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.3.539

    authors: Adachi S,Kawamura K,Takemoto K

    更新日期:1994-03-01 00:00:00

  • Notch-1 regulates transcription of the epidermal growth factor receptor through p53.

    abstract::The Notch pathway plays a key role in the development and is increasingly recognized for its importance in cancer. We demonstrated previously the overexpression of Notch-1 and its ligands in gliomas and showed that their knockdown inhibits glioma cell proliferation and survival. To elucidate the mechanisms downstream ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn079

    authors: Purow BW,Sundaresan TK,Burdick MJ,Kefas BA,Comeau LD,Hawkinson MP,Su Q,Kotliarov Y,Lee J,Zhang W,Fine HA

    更新日期:2008-05-01 00:00:00

  • CXCL1/GROα increases cell migration and invasion of prostate cancer by decreasing fibulin-1 expression through NF-κB/HDAC1 epigenetic regulation.

    abstract::Inflammatory tumor microenvironments play pivotal roles in the development of cancer. Inflammatory cytokines such as CXCL1/GROα exert cancer-promoting activities by increasing tumor angiogenesis. However, whether CXCL1/GROα also plays a role in the progression of prostate cancer, particularly in highly invasive castra...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs299

    authors: Kuo PL,Shen KH,Hung SH,Hsu YL

    更新日期:2012-12-01 00:00:00

  • Expression of cytochrome P450 in yeast after different chemical treatments.

    abstract::In Saccharomyces cerevisiae a number of chemical agents induce synthesis of cytochrome P450. A cytochrome P450 gene has been well characterized in this yeast: CYP51, which codes for a constitutive enzyme involved in the 14 alpha-demethylation of lanosterol, a key step in the biosynthesis of ergosterol. In this work, w...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/13.11.2175

    authors: Del Carratore R,Morichetti E,Cecchini E,Bronzetti G,Gallo E,Galeotti CL

    更新日期:1992-11-01 00:00:00

  • Effect of cAMP elevating compounds on inhibition of gap junctional communication and induction of morphological transformation in Syrian hamster embryo cells.

    abstract::An enhancement of the cellular cAMP level has been shown to protect against phorbol ester-induced inhibition of gap junctional intercellular communication (GJIC) and induction of morphological transformation in Syrian hamster embryo (SHE) cells. Cholera toxin, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and theophyl...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/13.10.1803

    authors: Roseng LE,Rivedal E,Sanner T

    更新日期:1992-10-01 00:00:00

  • Influence of phenobarbital on glycogen metabolism of rat liver pretreated with N-nitrosomorpholine.

    abstract::Sprague-Dawley rats were treated with N-nitrosomorpholine (NNM) alone (7 weeks, 120 mg/l in drinking water), with NNM followed by phenobarbital (PB) (750 mg/l for 6 weeks) or PB alone. The livers from these animals were investigated for glycogen content and activities of glucose-6-phosphatase, glucose-6-phosphate dehy...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/4.7.931

    authors: Mayer D,Moore MA,Bannasch P

    更新日期:1983-01-01 00:00:00