Correlation of polymorphic expression of CYP2D6 mRNA in bladder mucosa and tumor tissue to in vivo debrisoquine hydroxylase activity.

Abstract:

:Debrisoquine hydroxylase activity has been attributed to CYP2D6 and poor metabolizers of debrisoquine have a reduced relative risk of developing aggressive bladder cancer. Production of a proximate carcinogen could occur in liver or bladder mucosa. However, it is not known if CYP2D6 is expressed in human bladder mucosa. In vivo whole body debrisoquine hydroxylase activity was measured as the debrisoquine recovery ratio (DBRR) following single dose oral administration of debrisoquine (10 mg) in 10 normal subjects and 20 patients with bladder cancer prior to diagnostic cystoscopy. Semi-quantitative PCR was used to measure mRNA for CYP2D6 in bladder tissue obtained at cystoscopy. Of the 30 subjects, three were phenotypically and genotypically poor metabolizers. Among the extensive metabolizers, there were extensive intersubject variations in DBRR. A 10-fold variation in CYP2D6 mRNA levels was observed in bladder tissue. There was a highly significant association between DBRR and CYP2D6 mRNA expression (r2 = 0.702, P < 0.001). These results demonstrate the presence of CYP2D6 mRNA in bladder mucosa. Furthermore, they are consistent with debrisoquine hydroxylation being mediated by CYP2D6 and suggest that differences in mRNA concentration are rate limiting for enzyme activity and that bladder mucosal regulation reflects total body regulation for this enzyme. The expression of CYP2D6 in bladder mucosa suggests that this enzyme could be involved in the local production of a proximate carcinogen in this tissue and contribute to the pathogenesis of bladder cancer in man.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Romkes-Sparks M,Mnuskin A,Chern HD,Persad R,Fleming C,Sibley GN,Smith P,Wilkinson GR,Branch RA

doi

10.1093/carcin/15.9.1955

subject

Has Abstract

pub_date

1994-09-01 00:00:00

pages

1955-61

issue

9

eissn

0143-3334

issn

1460-2180

journal_volume

15

pub_type

杂志文章
  • Analysis of nucleotide excision repair by detection of single-stranded DNA transients.

    abstract::Nucleotide excision repair (NER) removes bulky DNA lesions and is thus crucial for the protection against environmental carcinogens and UV light exposure. Deficiencies in NER cause increased mutation rates and chromosomal aberrations. Current methods for studying NER are mostly based on either quantitation of lesion r...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/22.11.1789

    authors: Rubbi CP,Milner J

    更新日期:2001-11-01 00:00:00

  • Carcinogenicity studies of masheri, a pyrolysed product of tobacco.

    abstract::The carcinogenicity of two commonly used brown and black varieties of masheri, a pyrolysed tobacco product, was studied by feeding the masheri through the diet at a 10% level to three different animal species of both sexes. In Sprague-Dawley rats, only brown masheri was used, while in Swiss mice and Syrian golden hams...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/9.11.2137

    authors: Kulkarni JR,Lalitha VS,Bhide SV

    更新日期:1988-11-01 00:00:00

  • Dibenz[a,j]acridine metabolism: identification of in vitro products formed by liver microsomes from 3-methylcholanthrene-pretreated rats.

    abstract::The metabolism of the carcinogenic pentacyclic azaaromatic compound, dibenz[a,j]acridine, has been examined in liver microsomal incubations using preparations from 3-methylcholanthrene-pretreated Wistar rats. Using authentic synthetic standards, u.v. spectroscopy and mass spectrometry, the following were proved to be ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/7.8.1371

    authors: Gill JH,Duke CC,Rosario CA,Ryan AJ,Holder GM

    更新日期:1986-08-01 00:00:00

  • Enhancement of the invasive ability of a transformed human bronchial epithelial cell line by 12-O-tetradecanoyl-phorbol-13-acetate and diacylglycerol.

    abstract::The effect of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was studied using an immortalized human bronchial epithelial cell line, BEAS-2B, both in vivo and in vitro. The in vivo model consisted of tracheas reconstituted with an epithelium of BEAS-2B cells xenotransplanted into athymic nude mice. Int...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/10.12.2335

    authors: Bonfil RD,Momiki S,Fridman R,Reich R,Reddel R,Harris CC,Klein-Szanto A

    更新日期:1989-12-01 00:00:00

  • Monoclonal antibodies for the immunoassay of mutagenic compounds produced by cooking beef.

    abstract::A family of 2-amino-N-methylimidazoazaarene (AIA) mutagens are produced in meats by cooking, and are of concern as potential carcinogens in the human diet. These are potent genotoxins in bacterial mutation assays, but are present only in trace quantities in cooked foods. Conventional analytical chemistry methods have ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/9.1.153

    authors: Vanderlaan M,Watkins BE,Hwang M,Knize MG,Felton JS

    更新日期:1988-01-01 00:00:00

  • Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects.

    abstract::Human cancers are often associated with numerical and structural chromosomal instability. Structural chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBL) arise as consequences of direct DNA damage or due to replication on a damaged DNA template. In both cases, DNA repair is critical and inter-individual...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgv127

    authors: Vodicka P,Musak L,Frank C,Kazimirova A,Vymetalkova V,Barancokova M,Smolkova B,Dzupinkova Z,Jiraskova K,Vodenkova S,Kroupa M,Osina O,Naccarati A,Palitti F,Försti A,Dusinska M,Vodickova L,Hemminki K

    更新日期:2015-11-01 00:00:00

  • The effect of phorbols on metabolic cooperation between human fibroblasts.

    abstract::Autoradiography has been used to study the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), 4-O-methyl TPA, and phorbol on metabolic cooperation between human diploid fibroblasts. When the donors, hypoxanthine-guanine phosphoribosyl transferase+ (HGPRT+) cells, and recipients, HGPRT- cells, were plated together i...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.10.1207

    authors: Mosser DD,Bols NC

    更新日期:1982-01-01 00:00:00

  • Genetic variation and alterations of genes involved in NFκB/TNFAIP3- and NLRP3-inflammasome signaling affect susceptibility and outcome of colorectal cancer.

    abstract::Colorectal tumors are continuously exposed to an inflammatory environment, which together with mitogenic signals sustain several cancer hallmarks. Nuclear factor-kappa B (NFκB) is a major regulator of inflammation and variation in NFκB-associated genes could potentially be used as biomarkers to identify patients with ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/carcin/bgs256

    authors: Ungerbäck J,Belenki D,Jawad ul-Hassan A,Fredrikson M,Fransén K,Elander N,Verma D,Söderkvist P

    更新日期:2012-11-01 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...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/5.1.83

    authors: Zlotogorski C,Erickson LC

    更新日期:1984-01-01 00:00:00

  • Clinical potential role of circulating microRNAs in early diagnosis of colorectal cancer patients.

    abstract::Current procedures for diagnosis and biomarker examination of colorectal cancer (CRC) are invasive and unpleasant. There is a great need to identify sensitive and specific biomarkers for early diagnosis of CRC. Circulating microRNAs (miRNAs) are promising molecular markers for CRC prediction. We performed a comprehens...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/carcin/bgu189

    authors: Du M,Liu S,Gu D,Wang Q,Zhu L,Kang M,Shi D,Chu H,Tong N,Chen J,Adams TS,Zhang Z,Wang M

    更新日期:2014-12-01 00:00:00

  • Genetic variations in the transforming growth factor-beta pathway as predictors of survival in advanced non-small cell lung cancer.

    abstract::The magnitude of benefit is variable for advanced non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy. The purpose of this study is to determine whether genetic variations in the transforming growth factor-beta (TGF-β) pathway are associated with clinical outcomes in NSCLC patients receiv...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr067

    authors: Lin M,Stewart DJ,Spitz MR,Hildebrandt MA,Lu C,Lin J,Gu J,Huang M,Lippman SM,Wu X

    更新日期:2011-07-01 00:00:00

  • Urinary metabolites of N-nitrosodipropylamine, N-nitroso-2-hydroxypropylpropylamine and N-nitroso-2-oxopropylpropylamine in the rat.

    abstract::Analysis of 24 h urine samples of rats administered N-nitrosodipropylamine (NDPA), N-nitroso-2-hydroxypropylpropylamine (NHPPA) or N-nitroso-2-oxopropylpropylamine (NOPPA) showed that the major excretion product in each case was the beta-glucuronide of NHPPA. This conjugate was shown to be present at levels of about 5...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/2.9.859

    authors: Leung KH,Archer MC

    更新日期:1981-01-01 00:00:00

  • Hydrogen peroxide formation and DNA base modification by tumor promoter-activated polymorphonuclear leukocytes.

    abstract::This report shows that generation of hydrogen peroxide (H2O2) by human polymorphonuclear leukocytes (PMNs) activated with tumor promoters of varying potency as first and second stage promoters correlates well with activities of these promoters in vivo. Those tested were 12-O-tetradecanoylphorbol-13-acetate (TPA), a co...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.3.455

    authors: Frenkel K,Chrzan K

    更新日期:1987-03-01 00:00:00

  • 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

  • Comparison of arsenic-induced cell transformation, cytotoxicity, mutation and cytogenetic effects in Syrian hamster embryo cells in culture.

    abstract::Sodium arsenite and sodium arsenate were observed to induce morphological transformation of Syrian hamster embryo cells in a dose-dependent manner. A linear dose-dependence with a slope of approximately 1 was observed with both compounds when the data were plotted on a log-log graph. The trivalent sodium arsenite was ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.10.1421

    authors: Lee TC,Oshimura M,Barrett JC

    更新日期:1985-10-01 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...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.4.623

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

    更新日期:1999-04-01 00:00:00

  • Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens.

    abstract::Gastrointestinal tumours are among the most common malignancies in Western society, the majority of which are associated with dietary and lifestyle factors. Many dietary or lifestyle factors have been identified which may have toxic or carcinogenic properties. However, several dietary compounds also able to reduce gas...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg117

    authors: van der Logt EM,Roelofs HM,Nagengast FM,Peters WH

    更新日期:2003-10-01 00:00:00

  • Cell proliferation in nasal respiratory epithelium of people exposed to urban pollution.

    abstract::The nasal passages are a common portal of entry and are a prime site for toxicant-induced pathology. Sustained increases in regenerative cell proliferation can be a significant driving force in chemical carcinogenesis. The atmosphere in Mexico City contains a complex mixture of air pollutants and its residents are exp...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.3.383

    authors: Calderón-Garcidueñas L,Rodriguez-Alcaraz A,Garcia R,Barragan G,Villarreal-Calderón A,Madden MC

    更新日期:1999-03-01 00:00:00

  • Substituted hydroxyphenanthrenes in opium pyrolysates implicated in oesophageal cancer in Iran: structures and in vitro metabolic activation of a novel class of mutagens.

    abstract::Previous epidemiological and laboratory studies have indicated an association between the ingestion of opium pyrolysates, dietary deficiencies and the high incidence of oesophageal cancer in subjects in north-east Iran. Pyrolysates of opium, and particularly of morphine, a major opium alkaloid, were both shown to cont...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.10.1423

    authors: Friesen M,O'Neill IK,Malaveille C,Garren L,Hautefeuille A,Bartsch H

    更新日期:1987-10-01 00:00:00

  • Effect of chemical carcinogens on cholesterol biosynthetic pathways in the skin of mice.

    abstract::The metabolism of zymosterol and mevalonic acid was studied in vitro using the skin homogenates of 3-methylcholanthrene (3MC), diazacholesterol-treated and untreated mice. In normal mouse skin only lathosterol was a major metabolite and the other metabolites, cholesta-5,7,24-trien-3 beta-ol, desmosterol, cholesterol a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.9.1647

    authors: Tanimoto Y,Fukao K,Yoshiga K,Takada K,Ohyama Y,Okuda K

    更新日期:1990-09-01 00:00:00

  • N-acetoxy-N-acetyl-2-aminofluorene-induced mutation spectrum in a human hprt cDNA shuttle vector integrated into mammalian cells.

    abstract::The spectrum of mutations induced by N-acetoxy-N-acetyl-2-aminofluorene (N-AcO-AAF) was examined by the pZipHprtNeo shuttle vector in mammalian cells. The vector carries a cDNA of the human hypoxanthine phosphoribosyl transferase (hprt) gene, which is stably integrated into chromosomal DNA of a mouse cell line, VH12. ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.11.2245

    authors: Ogawa HI,Kimura H,Koya M,Higuchi H,Kato T

    更新日期:1993-11-01 00:00:00

  • Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1-/- mice.

    abstract::An ongoing controversy exists on beneficial versus harmful effects of high beta-carotene (BC) intake, especially for the lung. To elucidate potential mechanisms, we studied effects of BC on lung gene expression. We used a beta-carotene 15,15'-monooxygenase 1 (Bcmo1) knockout mouse (Bcmo1(-/-)) model, unable to convert...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgq083

    authors: van Helden YG,Godschalk RW,Heil SG,Bunschoten A,Hessel S,Amengual J,Bonet ML,von Lintig J,van Schooten FJ,Keijer J

    更新日期:2010-08-01 00:00:00

  • v-sis oncogene-induced transformation of human fibroblasts into cells capable of forming benign tumors.

    abstract::Normal human fibroblasts do not synthesize platelet-derived growth factor (PDGF), but they respond to its mitogenic action. In contrast, cells from several human fibrosarcomas have been shown to synthesize PDGF at significant levels. To investigate the possible role of PDGF expression in the development of tumors of m...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.10.2167

    authors: Yang D,Kohler SK,Maher VM,McCormick JJ

    更新日期:1994-10-01 00:00:00

  • Decreased expression of the glutathione S-transferases alpha and pi genes in human renal cell carcinoma.

    abstract::Using the polymerase chain reaction (PCR), a human kidney glutathione S-transferase (GST) alpha cDNA clone (GST alpha 12 K) was synthesized; it is identical to a known liver GST alpha cDNA clone except for one base change (G----A), indicating that an alpha class gene expressed in human kidney is similar to one express...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.12.2179

    authors: Klöne A,Weidner U,Hussnätter R,Harris J,Meyer D,Peter S,Ketterer B,Sies H

    更新日期:1990-12-01 00:00:00

  • Cyclin D1 gene polymorphism is associated with an increased risk of urinary bladder cancer.

    abstract::Cyclin D1 is believed to play an important role in the genesis and/or progression of transitional cell cancer (TCC) of the urinary bladder. Cyclin D1 gene (CCND1) mRNA is alternatively spliced to produce two transcripts, and the splicing pattern may be modulated by a G to A single nucleotide polymorphism within the sp...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.2.257

    authors: Wang L,Habuchi T,Takahashi T,Mitsumori K,Kamoto T,Kakehi Y,Kakinuma H,Sato K,Nakamura A,Ogawa O,Kato T

    更新日期:2002-02-01 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...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.1.89

    authors: Holmes EH

    更新日期:1990-01-01 00:00:00

  • Potential carcinogenicity of 5,6-dimethoxysterigmatocystin in rats.

    abstract::The potential carcinogenic activity of 5,6-dimethoxysterigmatocystin (DMSC) was examined by oral administration in rats. In Experiment I, all of eight effective ACI/N rats given DMSC in the diet at a concentration of 50 p.p.m. developed neoplastic nodules of the liver. Five rats developed hepatocellular carcinomas and...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/9.6.1039

    authors: Mori H,Sugie S,Yoshimi N,Kuniyasu T,Iwata H,Kawai K,Hamasaki T

    更新日期:1988-06-01 00:00:00

  • In vivo accumulation of 8-hydroxy-2'-deoxyguanosine in DNA correlates with release of reactive oxygen species in Fanconi's anaemia families.

    abstract::The present study was aimed at verifying the occurrence, if any, of in vivo oxidative DNA damage in FA homozygotes, their parents and siblings. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was measured, by HPLC/EC, in DNA from circulating blood leucocytes from FA homozygotes and their relatives and compared with a group of pa...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.4.735

    authors: Degan P,Bonassi S,De Caterina M,Korkina LG,Pinto L,Scopacasa F,Zatterale A,Calzone R,Pagano G

    更新日期:1995-04-01 00:00:00

  • Ellagic acid induces transcription of the rat glutathione S-transferase-Ya gene.

    abstract::Induction of glutathione S-transferase (GST) enzymes can increase detoxification of carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis. To determine if the anticarcinogen ellagic acid induces cellular enzymes which detoxify carcinogens, we examined the effect of ellagic acid on the expression of g...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.3.665

    authors: Barch DH,Rundhaugen LM,Pillay NS

    更新日期:1995-03-01 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