Cyclooxygenase-2, malondialdehyde and pyrimidopurinone adducts of deoxyguanosine in human colon cells.

Abstract:

:Cyclooxygenases (COX) catalyse the oxygenation of arachidonic acid to prostaglandin (PG) endoperoxides. Activity of one of the COX isoforms, COX-2, results in production of prostaglandin E(2) (PGE(2)) via the endoperoxide PGH(2). COX-2 has been implicated in the pathogenesis of colorectal cancer. Malondialdehyde (MDA) is a mutagen produced by spontaneous and enzymatic breakdown of PGH(2). MDA reacts with DNA to form adducts, predominantly the pyrimidopurinone adduct of deoxyguanosine (M(1)G). Here the hypothesis was tested that COX-2 activity in human colon cells results in formation of MDA and generation of M(1)G adducts. M(1)G was detected in basal cultures of human non-malignant colon epithelial (HCEC) and malignant SW48, SW480, HT29 and HCA-7 colon cells, at levels from 77 to 148 adducts/10(8) nucleotides. Only HCA-7 and HT29 cells expressed COX-2 protein. Levels of M(1)G correlated significantly (r = 0.98, P < 0.001) with those of intracellular MDA determined colorimetrically in the four malignant cell types, but neither parameter correlated with expression of COX-2 or PG biosynthesis. Induction of COX-2 expression by phorbol 12-myristate 13-acetate in HCEC cells increased PGE(2) production 20-fold and MDA concentration 3-fold. Selective inhibition of COX-2 activity in HCA-7 cells by NS-398 significantly inhibited PGE(2) production, but altered neither MDA nor M(1)G levels. Malondialdehyde treatment of HCEC cells resulted in a doubling of M(1)G levels. These results show for the first time in human colon cells that COX-2 activity is associated with formation of the endogenous mutagen, MDA. Moreover, they demonstrate the correlation between MDA concentration and M(1)G adduct levels in malignant cells.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Sharma RA,Gescher A,Plastaras JP,Leuratti C,Singh R,Gallacher-Horley B,Offord E,Marnett LJ,Steward WP,Plummer SM

doi

10.1093/carcin/22.9.1557

keywords:

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

1557-60

issue

9

eissn

0143-3334

issn

1460-2180

journal_volume

22

pub_type

杂志文章
  • Transforming growth factors induce markers of neoplasia in cultured adult rat bladder.

    abstract::Transforming growth factors alpha and beta (TGF-alpha and TGF-beta) isolated from normal mouse kidney induced gross morphological changes in rat urothelial cells maintained in organ culture. These morphological effects are similar to those observed after long-term treatment of rat bladder organ cultures with the carci...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.4.595

    authors: Knowles MA,Hicks RM,Dave H,Harvey AE,Roberts AB,Sporn MB

    更新日期:1985-04-01 00:00:00

  • SH3RF2 functions as an oncogene by mediating PAK4 protein stability.

    abstract::SH3RF (SH3-domain-containing RING finger protein) family members, SH3RF1-3, are multidomain scaffold proteins involved in promoting cell survival and apoptosis. In this report, we show that SH3RF2 is an oncogene product that is overexpressed in human cancers and regulates p21-activated kinase 4 (PAK4) protein stabilit...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgt338

    authors: Kim TW,Kang YK,Park ZY,Kim YH,Hong SW,Oh SJ,Sohn HA,Yang SJ,Jang YJ,Lee DC,Kim SY,Yoo HS,Kim E,Yeom YI,Park KC

    更新日期:2014-03-01 00:00:00

  • DNA and hemoglobin alkylation by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in F344 rats.

    abstract::Alkylation of DNA and hemoglobin was compared in male F344 rats given a single s.c. injection of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), or its major metabolite formed by carbonyl reduction, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). In hepatic DNA, levels of 7...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/9.9.1665

    authors: Hecht SS,Trushin N

    更新日期:1988-09-01 00:00:00

  • HIF-2alpha-mediated activation of the epidermal growth factor receptor potentiates head and neck cancer cell migration in response to hypoxia.

    abstract::Despite their individual key roles in promoting head and neck squamous cell carcinoma (HNSCC) progression and treatment resistance, little is known about the impact of intratumoral hypoxia on the activity of the epidermal growth factor receptor (EGFR) signaling pathway in this cancer type. Here, we show that in highly...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgq078

    authors: Wang X,Schneider A

    更新日期:2010-07-01 00:00:00

  • Steroid hormone receptor expression and proliferation in rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

    abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary gland carcinogen present in the human diet. Herein, the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ER beta) and progesterone receptor (PR) was examined in mammary gland carcinomas induced by PhIP in female Sprague-Dawley ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi013

    authors: Qiu C,Shan L,Yu M,Snyderwine EG

    更新日期:2005-04-01 00:00:00

  • Inhibition of 7,12-dimethylbenz[a]anthracene-induced lung tumorigenesis in A/J mice by food restriction is reversed by adrenalectomy.

    abstract::Prior work has demonstrated that food restriction of mice markedly suppresses 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion of skin papillomas and adrenalectomy prior to initiating food restriction completely reverses the tumor inhibitory effect of underfeeding. In the present experiment the effect of food rest...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.2.209

    authors: Pashko LL,Schwartz AG

    更新日期:1996-02-01 00:00:00

  • Mutations in the Ha-ras proto-oncogene in spontaneous and chemically induced liver tumours of the CF1 mouse.

    abstract::Mutations in codon 61 of the Ha-ras proto-oncogene have been shown to occur with a high frequency in both spontaneous and carcinogen-induced liver tumours of the B6C3F1 mouse. In the present study we analysed the frequency and pattern of Ha-ras mutations in liver tumours in a different strain of mice, namely the CF1 m...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.10.1875

    authors: Bauer-Hofmann R,Buchmann A,Wright AS,Schwarz M

    更新日期:1990-10-01 00:00:00

  • Urinary levels of volatile organic carcinogen and toxicant biomarkers in relation to lung cancer development in smokers.

    abstract::Besides polycyclic aromatic hydrocarbons (PAH) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which are established lung carcinogens, tobacco smoke also contains relatively large quantities of volatile organic carcinogens and toxicants, including 1,3-butadiene, ethylene oxide, benzene, acrolein and crotonal...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs026

    authors: Yuan JM,Gao YT,Wang R,Chen M,Carmella SG,Hecht SS

    更新日期:2012-04-01 00:00:00

  • 2-Nitrofluorene metabolism in the rat lung. Pharmacokinetic and metabolic effects of beta-naphthoflavone treatment.

    abstract::Absorption, metabolism and DNA binding of 2-nitrofluorene (NF) was studied in isolated, perfused and ventilated rat lungs and in lung microsomal incubations. Comparisons were made between control animals and animals treated with beta-naphthoflavone (BNF), a 2,3,7,8-tetrachlorodibenzo(rho)dioxin (TCDD) receptor ligand ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.8.1249

    authors: Törnquist S,Möller L,Gabrielsson J,Gustafsson JA,Toftgård R

    更新日期:1990-08-01 00:00:00

  • Oxidation of 5'-site guanine at GG and GGG sequences induced by a metabolite of carcinogenic heterocyclic amine PhIP in the presence of Cu(II) and NADH.

    abstract::Adduct formation has been considered to be a major causal factor of DNA damage by carcinogenic heterocyclic amines. By means of experiments with an electrochemical detector coupled to a high-performance liquid chromatograph, we revealed that N-hydroxy metabolite of 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (Ph...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.5.855

    authors: Murata M,Kawanishi S

    更新日期:2002-05-01 00:00:00

  • 4-Hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers in mice: characterization of FHIT and survivin expression and chemopreventive effects of indomethacin.

    abstract::The administration of 4-hydroxybutyl(butyl)nitrosamine (OH-BBN) to male B6D2F1 mice yielded a high incidence of large palpable urinary bladder cancers. Since prior studies demonstrated chemopreventive effects of non-steroidal anti-inflammatory drugs (NSAIDs), we further explored the efficacy of the NSAID indomethacin ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgh352

    authors: Lubet RA,Huebner K,Fong LY,Altieri DC,Steele VE,Kopelovich L,Kavanaugh C,Juliana MM,Soong SJ,Grubbs CJ

    更新日期:2005-03-01 00:00:00

  • Metabolism of benzo[a]pyrene and DNA adduct formation in cultured human epidermal keratinocytes.

    abstract::Cultured human epidermal cells which require no feeder layer were used to study metabolism of benzo[a]pyrene (BP) and DNA adduct formation. The cultures were prepared from a single cell suspension and maintained at a pH of 5.9--6.2. At 2 microM BP some cell toxicity was observed, and substantial cell death occurred at...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/2.7.581

    authors: Theall G,Eisinger M,Grunberger D

    更新日期:1981-01-01 00:00:00

  • Effects produced by the non-genotoxic hepatocarcinogen methylclofenapate in dwarf mice: peroxisome induction uncoupled from DNA synthesis and nuclearity changes.

    abstract::Both Snell dwarf mice (dw/dw) and their phenotypically normal heterozygotes (dw/+) were dosed with methylclofenapate (MCP) at daily intervals by gavage (25 mg/kg). Animals were killed at 12, 24, 36 and 72 h after the initial dose and the parameters of ploidy, nuclearity and DNA synthesis were measured in hepatocytes i...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.3.387

    authors: Styles JA,Kelly MD,Pritchard NR,Foster JR

    更新日期:1990-03-01 00:00:00

  • The mycotoxin aflatoxin B1 stimulates Epstein-Barr virus-induced B-cell transformation in in vitro and in vivo experimental models.

    abstract::Although Epstein-Barr virus (EBV) infection is widely distributed, certain EBV-driven malignancies are geographically restricted. EBV-associated Burkitt's lymphoma (eBL) is endemic in children living in sub-Saharan Africa. This population is heavily exposed to food contaminated with the mycotoxin aflatoxin B1 (AFB1). ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgv142

    authors: Accardi R,Gruffat H,Sirand C,Fusil F,Gheit T,Hernandez-Vargas H,Le Calvez-Kelm F,Traverse-Glehen A,Cosset FL,Manet E,Wild CP,Tommasino M

    更新日期:2015-11-01 00:00:00

  • Abnormal response of ataxia-telangiectasia cells to agents that break the deoxyribose moiety of DNA via a targeted free radical mechanism.

    abstract::A defect in DNA repair coupled to anomalous DNA synthesis after induction of certain radiogenic DNA damage is suspected to underlie the radiosensitivity of cells from patients with ataxia-telangiectasia (A-T). The response of cultured skin fibroblasts from A-T patients and A-T heterozygotes to six agents inducing vari...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/4.10.1317

    authors: Shiloh Y,Tabor E,Becker Y

    更新日期:1983-10-01 00:00:00

  • Ultrastructural analysis of pancreatic carcinogenesis. V. Changes in differentiation of acinar cells during chronic treatment with N-nitrosobis(2-hydroxypropyl)amine.

    abstract::An electron microscope study was carried out on changes in the pancreatic acinar tissues of male Syrian hamsters during the course of induction of pancreatic neoplasia by lifetime weekly injections of N-nitroso-bis(2-hydroxypropyl)amine (BHP). The dominant process observed was a loss of differentiation of the acinar c...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.5.485

    authors: Flaks B,Moore MA,Flaks A

    更新日期:1982-01-01 00:00:00

  • Ultrastructural and biochemical alterations induced by tryptophan pyrolysis products on rat hepatocytes in primary culture. I. Action on the transcriptional process.

    abstract::Adult rat hepatocytes in primary culture were used to study the effect of tryptophan pyrolysis products on the transcriptional process. Hepatocytes were treated with 1, 5 and 10 micrograms/ml of 3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]-indole (Trp-P-1) or 3-amino-1-methyl-5H-pyrido-[4,3-b]-indole (Trp-P-2) for 2 and 4 h...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/4.4.481

    authors: Thybaud-Lambay V,Decloitre F,Moulé Y,Florentin Y

    更新日期:1983-01-01 00:00:00

  • Dose and schedule of oral retinoic acid and indomethacin needed to effectively inhibit phorbol ester-induced epidermal ornithine decarboxylase activity.

    abstract::Currently there is no well-defined biological parameter or marker to help define agents, doses, and dose schedules for human cancer chemoprevention trials. Induction of ornithine decarboxylase, the rate limiting enzyme in the polyamine biosynthetic pathway, has been shown to be an essential aspect of mouse skin tumor ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.11.1589

    authors: Loprinzi CL,Verma AK

    更新日期:1985-11-01 00:00:00

  • Induction of mammalian cell transformation and genotoxicity by 2-methoxyestradiol, an endogenous metabolite of estrogen.

    abstract::2-methoxyestradiol (2-MeOE(2)) is an endogenous metabolite of 17beta-estradiol and a proposed inhibitor of tumor growth and angiogenesis. However, 2-MeOE(2) is also an inhibitor of microtubule assembly and other microtubule inhibitors, e.g. colcemid and diethylstilbestrol, induce aneuploidy and cell transformation in ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/21.4.735

    authors: Tsutsui T,Tamura Y,Hagiwara M,Miyachi T,Hikiba H,Kubo C,Barrett JC

    更新日期:2000-04-01 00:00:00

  • Tumor progression and metastasis.

    abstract::It is now widely accepted that cancer is attributed to the accumulation of genetic alterations in cells. Thus, to understand the molecular mechanisms of cancer metastasis, it is indispensable to identify the genes whose alterations accumulate during cancer progression as well as the genes whose expression is responsib...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/21.3.497

    authors: Yokota J

    更新日期:2000-03-01 00:00:00

  • DNA damage caused by reactive oxygen species originating from a copper-dependent oxidation of the 2-hydroxy catechol of estradiol.

    abstract::It has previously been proposed that redox cycling between catechol estrogens and their quinones, mediated by cytochrome P450, could lead to the generation of free radicals that would subsequently cause oxidative damage to DNA and proteins that might have a role in hormonal carcinogenesis. Alternative, non-enzymatic m...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.7.1421

    authors: Li Y,Trush MA,Yager JD

    更新日期:1994-07-01 00:00:00

  • Small molecules that bind the Mdm2 RING stabilize and activate p53.

    abstract::p53 is a tumor suppressor that responds to a variety of stresses such as oncogenes and DNA damage by activating its transcriptional targets to allow repair or elimination of damaged cells. In the absence of stress signals, p53 needs to be kept in check and this is achieved by the E3 ligase MDM2. For tumors that retain...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs092

    authors: Roxburgh P,Hock AK,Dickens MP,Mezna M,Fischer PM,Vousden KH

    更新日期:2012-04-01 00:00:00

  • Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.

    abstract::Common genetic variation may play an important role in altering lung cancer risk. We conducted a pathway-based candidate gene evaluation to identify genetic variations that may be associated with lung cancer in a population-based case-control study in Xuan Wei, China (122 cases and 111 controls). A total of 1260 singl...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn178

    authors: Hosgood HD 3rd,Menashe I,Shen M,Yeager M,Yuenger J,Rajaraman P,He X,Chatterjee N,Caporaso NE,Zhu Y,Chanock SJ,Zheng T,Lan Q

    更新日期:2008-10-01 00:00:00

  • Aphidicolin-sensitive DNA repair synthesis in human fibroblasts damaged with bleomycin is distinct from UV-induced repair.

    abstract::Human fibroblasts repair DNA damaged by bleomycin through both short-patch and long-patch pathways, mediated by an aphidicolin-resistant (beta) and aphidicolin-sensitive (delta) DNA polymerase respectively (DiGiuseppe, J.A. and Dresler, S.L. (1989) Biochemistry, 28, 9515-9520). Despite certain similarities, aphidicoli...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.6.1021

    authors: DiGiuseppe JA,Hunting DJ,Dresler SL

    更新日期:1990-06-01 00:00:00

  • Cell cross-talk mediates PPARalpha null hepatocyte proliferation after peroxisome proliferator exposure.

    abstract::Peroxisome proliferator activated receptor(alpha) (PPARalpha) mediates the liver's responses to peroxisome proliferator compounds. These responses include induction of specific hepatic enzymes, peroxisome proliferation and hepatocyte proliferation. PPARalpha null mice, which lack receptor in all cells of the body, do ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg180

    authors: Weglarz TC,Sandgren EP

    更新日期:2004-01-01 00:00:00

  • Tumor-initiating activity, mutagenicity, and metabolism of methylated anthracenes.

    abstract::Specific methylated derivatives of anthracene are mutagenic in S. typhimurium and have tumor-initiating activity on mouse skin. In this study, the mutagenic activities of 1-, 2-, and 9-methylanthracene, 2,9- and 9,10-dimethylanthracene, 2,9,-10-trimethylanthracene, 2,3,9,10-tetramethylanthracene, and the photo-oxide o...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.10.1483

    authors: La Voie EJ,Coleman DT,Rice JE,Geddie NG,Hoffmann D

    更新日期:1985-10-01 00:00:00

  • Epigenetic therapy using the histone deacetylase inhibitor for increasing therapeutic gain in oral cancer: prevention of radiation-induced oral mucositis and inhibition of chemical-induced oral carcinogenesis.

    abstract::In addition to genetic changes, epigenetic aberrations also play important roles in radiation- and chemical-induced disorders and carcinogenesis. The present study investigated whether epigenetic therapy with a histone deacetylase (HDAC) inhibitor has dual benefits for radiation-induced oral mucositis and chemical-ind...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgp079

    authors: Chung YL,Lee MY,Pui NN

    更新日期:2009-08-01 00:00:00

  • The DNA binding activity of the liver transcription factors LFB1 (HNF1) and HNF4 varies coordinately in rat hepatocellular carcinoma.

    abstract::As renal cell carcinomas are characterized by the disappearance of the transcription factor LFB1, which is known to be primarily involved in gene regulation in the liver, we have measured the presence of LFB1 in rat hepatocellular carcinomas induced by diethylnitrosamine. The level of LFB1 binding activity in adenoid-...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.1.143

    authors: Stumpf H,Senkel S,Rabes HM,Ryffel GU

    更新日期:1995-01-01 00:00:00

  • Selenium and the genesis of murine mammary tumors.

    abstract::One hundred forty-seven female Sprague-Dawley rats were divided into 5 groups and at 60 days of age were treated i.g. with 5 mg of 7,12-dimethylbenzanthracene (DMBA) suspended in 1.0 ml of sesame oil. Selenium (Se), as selenium dioxide (SeO2), was administered in the drinking water to 4 of the 5 groups (30 rats/group)...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/2.6.519

    authors: Welsch CW,Goodrich-Smith M,Brown CK,Greene HD,Hamel EJ

    更新日期:1981-01-01 00:00:00

  • A study of endonuclease III-sensitive sites in irradiated DNA: detection of alpha-particle-induced oxidative damage.

    abstract::An important difference between chemical agents that induce oxidative damage in DNA and ionizing radiation is that radiation-induced damage is clustered locally on the DNA. Both modelling and experimental studies have predicted the importance of clustering of lesions induced by ionizing radiation and its dependence on...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.5.905

    authors: Prise KM,Pullar CH,Michael BD

    更新日期:1999-05-01 00:00:00