Comparison of hydrocarbon-DNA adducts formed in mouse skin in vivo and in organ culture in vitro following treatment with benzo[a]pyrene.

Abstract:

:Species differences in the metabolism of toxic chemicals can confound the extrapolation of experimentally determined risk data to man. However, it is often difficult to obtain reliable information on human metabolism, particularly of genotoxic agents. In this study, comparisons of chromatographic profiles of DNA adducts formed in vivo and in vitro have been applied to develop and validate in vitro systems as models for the bioactivation of precursor genotoxic agents in vivo. Reversed phase h.p.l.c. analysis showed that the DNA adducts obtained from the skin (epidermal and dermal) of mice (CD1, CF1 and athymic nude mice) treated topically with [3H] or [14C]benzo[a]pyrene (BP) were qualitatively very similar to those formed in mouse (CD1) skin explant cultures. In each case the principal product was the N2-deoxyguanosine adduct, (+)-N2-(7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo[a]-pyrene-10S- yl)-2'-deoxyguanosine, derived from (+)-7R,8S-dihydroxy-9R,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. The use of [14C]BP has provided an accurate reference profile of BP-DNA adducts formed in mouse skin in vivo. These findings show that mouse skin explants maintained in organ culture effectively mimic the bioactivation of BP and the binding of the products to the DNA of mouse skin in vivo. Such culture techniques are readily transferable to human skin thus permitting the indirect determination of bioactivation pathways in human skin in vivo for comparison with those of mouse skin and other models used to determine the human hazard. In principle, this approach to validate in vitro bioactivation systems may be applied to all human tissues.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Huckle KR,Smith RJ,Watson WP,Wright AS

doi

10.1093/carcin/7.6.965

subject

Has Abstract

pub_date

1986-06-01 00:00:00

pages

965-70

issue

6

eissn

0143-3334

issn

1460-2180

journal_volume

7

pub_type

杂志文章
  • Induction of humoral immunity toward 2-acetylaminofluorene in mice: modulation of DNA binding after 4 weeks dietary exposure to the carcinogen.

    abstract::In order to investigate the modulatory effect of the immune response induced by recurrent carcinogen exposure, anti-2-acetylaminofluorene (anti-2-AAF) IgG were elicited in Swiss mice before subsequent carcinogen administration. The immunization schedule consisted of three weekly i.p. injections of 2-acetylaminofluoren...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.8.1705

    authors: Verdina A,Zito R,Cortese G,Leopardi P,Marcon F,Zijno A,Crebelli R

    更新日期:1996-08-01 00:00:00

  • Effects of arsenic on telomerase and telomeres in relation to cell proliferation and apoptosis in human keratinocytes and leukemia cells in vitro.

    abstract::Telomeres are critical in maintaining chromosome and genomic stability. Arsenic, a human carcinogen as well as an anticancer agent, is known for its clastogenicity. To better understand molecular mechanisms of arsenic actions, we investigated arsenite effects on telomere and telomerase and determined cell growth and a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg141

    authors: Zhang TC,Schmitt MT,Mumford JL

    更新日期:2003-11-01 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...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs265

    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

  • Evidence for a 2,3-epoxide as an intermediate in the microsomal metabolism of 6-nitrobenzo[a]pyrene.

    abstract::The rat liver microsomal metabolism of 3-deutero-6-nitrobenzo(a)pyrene ([3-2H]6-NO2-BaP) was studied. The metabolites were separated by h.p.l.c. The 500 MHz 1H n.m.r. spectral analysis of the metabolites indicated that the 3-hydroxy-6-NO2-BaP and 6-NO2-BaP-3,9-hydroquinone each retained 33% of the deuterium label at t...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/4.6.699

    authors: Chou MW,Evans FE,Yang SK,Fu PP

    更新日期:1983-01-01 00:00:00

  • Human O(6)-alkylguanine-DNA alkyltransferase: protection against alkylating agents and sensitization to dibromoalkanes.

    abstract::O(6)-alkylguanine-DNA alkyltransferase (AGT) is a suicide protein that corrects DNA damage by alkylating agents and may also serve to activate environmental carcinogens. We expressed human wild-type and two active mutant AGTs in bacteria that lack endogenous AGT and are also defective in nucleotide excision repair, to...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.11.2089

    authors: Abril N,Luque-Romero FL,Christians FC,Encell LP,Loeb LA,Pueyo C

    更新日期:1999-11-01 00:00:00

  • Influence of 15 retinoic acid amides on urinary bladder carcinogenesis in the mouse.

    abstract::A series of experiments was conducted to determine the efficacy of 15 synthetic retinoic acid amides (retinamides) as inhibitors of chemical carcinogenesis of the urinary bladder in C57BL/6 x DBA/2F1 mice. Eight of the retinamides tested had significant protective activity when administered at nontoxic levels in the d...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.12.1469

    authors: Moon RC,McCormick DL,Becci PJ,Shealy YF,Frickel F,Paust J,Sporn MB

    更新日期:1982-01-01 00:00:00

  • Molecular analysis of mutations induced by 2-chloroacetaldehyde, the ultimate carcinogenic form of vinyl chloride, in human cells using shuttle vectors.

    abstract::Vinyl chloride (VC) is a carcinogen associated with human and animal cancers. The ultimate carcinogenic form of VC, 2-chloroacetaldehyde (CAA), has been suspected to be mutagenic and we confirmed the mutagenicity of CAA using a modified shuttle vector plasmid. Base sequence analyses of 109 mutant plasmids with mutatio...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.10.2389

    authors: Matsuda T,Yagi T,Kawanishi M,Matsui S,Takebe H

    更新日期:1995-10-01 00:00:00

  • Modulation of glutathione content and the effect on methionine auxotrophy and cellular distribution of homocysteine and cysteine in mouse cell lines.

    abstract::The inability of cells in culture to grow in medium where methionine is replaced by its metabolic precursor, homocysteine, has been linked to neoplastic transformation and termed 'methionine dependence' or 'methionine auxotrophy'. The present investigation was undertaken to establish the influence of intracellular glu...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.2.241

    authors: Djurhuus R,Svardal AM,Mansoor MA,Ueland PM

    更新日期:1991-02-01 00:00:00

  • Med1 plays a critical role in the development of tamoxifen resistance.

    abstract::Understanding the molecular pathways that contribute to the development of tamoxifen resistance is a critical research priority as acquired tamoxifen resistance is the principal cause of poor prognosis and death of patients with originally good prognosis hormone-responsive breast tumors. In this report, we provide evi...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs105

    authors: Nagalingam A,Tighiouart M,Ryden L,Joseph L,Landberg G,Saxena NK,Sharma D

    更新日期:2012-04-01 00:00:00

  • Development of a syngeneic mouse model for events related to ovarian cancer.

    abstract::Mouse ovarian surface epithelial cells (MOSEC) were obtained from virgin, mature mice by mild trypsinization and were repeatedly passaged in vitro. Early passage cells (<20 passages) exhibited a cobblestone morphology and contact inhibition of growth. After approximately 20 passages in vitro, cobblestone morphology an...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/21.4.585

    authors: Roby KF,Taylor CC,Sweetwood JP,Cheng Y,Pace JL,Tawfik O,Persons DL,Smith PG,Terranova PF

    更新日期:2000-04-01 00:00:00

  • The relationship between the carcinogenicity and mutagenicity of nitrosamines in a hepatocyte-mediated mutagenicity assay.

    abstract::A quantitative relationship was established for 26 nitrosamines between their carcinogenic effectiveness in experimental animals and their mutagenic activity in a mammalian cell-mediated assay. Mutagenesis was measured in Chinese hamster V79 cells co-cultivated with primary rat hepatocytes, which are capable of activa...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/2.10.1075

    authors: Jones CA,Marlino PJ,Lijinsky W,Huberman E

    更新日期:1981-01-01 00:00:00

  • Isolation of clones displaying enhanced resistance to methylating agents in O6-methylguanine-DNA methyltransferase-proficient CHO cells.

    abstract::O6-Methylguanine-DNA methyltransferase (MT)-proficient Chinese hamster ovary cells were grown in the presence of low, gradually increasing levels of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) with the aim of selecting MNNG-resistant cell lines. Six resistant clones with two levels of resistance were isolated. A 3-fol...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/9.7.1217

    authors: Aquilina G,Frosina G,Zijno A,Di Muccio A,Dogliotti E,Abbondandolo A,Bignami M

    更新日期:1988-07-01 00:00:00

  • DNA adducts, detected by 32P-postlabelling, in DNA treated in vitro with bile from patients with familial adenomatous polyposis and from unaffected controls.

    abstract::Patients with familial adenomatous polyposis (FAP) have a high risk of developing duodenal adenomas and carcinomas. The distribution of these neoplasms resembles mucosal exposure to bile, suggesting that bile may play a role in adenoma development. Our previous results, using DNA adducts detected by 32P-postlabelling ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.6.1107

    authors: Scates DK,Spigelman AD,Nugent KP,Phillips RK,Venitt S

    更新日期:1993-06-01 00:00:00

  • Role for EPS8 in squamous carcinogenesis.

    abstract::We have investigated the role of the signaling intermediate, EPS8, in tumor progression using a model system and in vivo. HN4 primary tumor cells express low levels of EPS8, similar to normal keratinocytes, and show minimal invasion in vitro in response to epidermal growth factor, whereas HN12 cells express high level...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn252

    authors: Wang H,Patel V,Miyazaki H,Gutkind JS,Yeudall WA

    更新日期:2009-01-01 00:00:00

  • Increased levels of the HER1 adaptor protein Rukl/CIN85 contribute to breast cancer malignancy.

    abstract::The adaptor protein regulator for ubiquitous kinase/c-Cbl-interacting protein of 85kDa (Ruk/CIN85) was found to modulate HER1/EGFR signaling and processes like cell adhesion and apoptosis. Although these features imply a role in carcinogenesis, it is so far unknown how and by which molecular mechanisms Ruk/CIN85 could...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs228

    authors: Samoylenko A,Vynnytska-Myronovska B,Byts N,Kozlova N,Basaraba O,Pasichnyk G,Palyvoda K,Bobak Y,Barska M,Mayevska O,Rzhepetsky Y,Shuvayeva H,Lyzogubov V,Usenko V,Savran V,Volodko N,Buchman V,Kietzmann T,Drobot L

    更新日期:2012-10-01 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

  • Mutagenicity of 3'-methyl-N,N-dimethyl-4-amino azobenzene metabolites and related compounds.

    abstract::To elucidate the mechanism of metabolic activation of 3'-methyl-N,N-dimethyl-4-aminoazobenzene (3'-Me-DAB), the mutagenicity of its metabolites and some related azo compounds towards Salmonella typhimurium TA-98 and TA-100 was investigated. Mutagenicity of the metabolites, either N-demethylated or oxidized at the 3'-m...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/1.2.121

    authors: Mori Y,Niwa T,Hori T,Toyoshi K

    更新日期:1980-02-01 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

  • Prostate specific antigen and androgen receptor induction and characterization of an immortalized adult human prostatic epithelial cell line.

    abstract::Progress in prostate cancer research has been hindered by the lack of well characterized, immortalized, human prostatic epithelial cell lines that express markers of normal prostatic epithelial cells and mimic normal growth and differentiation responses to androgens. The objectives of this study were to: (i) establish...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.8.1641

    authors: Webber MM,Bello D,Kleinman HK,Wartinger DD,Williams DE,Rhim JS

    更新日期:1996-08-01 00:00:00

  • Tissue levels of S-adenosylmethionine and S-adenosylhomocysteine in rats fed methyl-deficient, amino acid-defined diets for one to five weeks.

    abstract::The levels of S-adenosylmethionine (AdoMet) and of S-adenosylhomocysteine (AdoHcy) as well as the ratio of AdoMet/AdoHcy were determined in the liver, lungs, testes and kidneys of weanling male rats fed a commercial chow diet or 5 different amino acid-defined diets for 1-5 weeks. The amino acid-defined diets used were...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/4.8.1051

    authors: Shivapurkar N,Poirier LA

    更新日期:1983-08-01 00:00:00

  • Carcinogen metabolism in cultured human tissues and cells.

    abstract::A large number of chemical carcinogens require metabolic activation before they are biologically active. The metabolism of a few of these compounds has been investigated in cultured human tissues and cells and the metabolism has been compared with the metabolism in organs from experimental animals in which the compoun...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/11.5.707

    authors: Autrup H

    更新日期:1990-05-01 00:00:00

  • Covalent binding of styrene to DNA in rat and mouse.

    abstract::Covalent binding of [7-3H]styrene (S) to DNA in vivo was measured and evaluated in a quantitative manner in order to investigate whether DNA adduct formation could form a mechanistic basis for tumor induction in a carcinogenicity bioassay. [7-3H]S was administered by inhalation in a closed chamber to male and female C...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.3.355

    authors: Cantoreggi S,Lutz WK

    更新日期:1993-03-01 00:00:00

  • Limited capacity for the removal of O6-methylguanine and its regeneration in a human lymphoma line.

    abstract::The Raji human lymphoma line is able to remove O6-methylguanine (O6MeG) lesions introduced by treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The reaction has a rapid phase in which approximately 40% of the O6MeG is removed in the first 10 min. The capacity of cells for rapid O6MeG removal is limi...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/2.12.1293

    authors: Sklar R,Brady K,Strauss B

    更新日期:1981-01-01 00:00:00

  • Metabolism of benzo[a]pyrene by cultured human hepatocytes from multiple donors.

    abstract::Primary hepatocyte cultures from six human donors were established and their abilities to metabolize the polycyclic aromatic hydrocarbon carcinogen benzo[a]pyrene (B[a]P) were examined. Cells from each donor were plated at similar densities (1 X 10(7) cells/100 mm dish). All cultures metabolized B[a]P to a significant...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/5.12.1577

    authors: Moore CJ,Gould MN

    更新日期:1984-12-01 00:00:00

  • gamma-Glutamyltranspeptidase-positive rat hepatocytes are protected from GSH depletion, oxidative stress and reversible alterations of collagen receptors.

    abstract::The aim of this study has been to define cytotoxic mechanisms that may cause clonal expansion in the liver of pre-carcinogenic cells. An in vitro model, which has been described previously, was used. Hepatocytes were isolated from carcinogen-treated rats and a high proportion of the cells were gamma-glutamyltranspepti...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.1.69

    authors: Stenius U,Rubin K,Gullberg D,Högberg J

    更新日期:1990-01-01 00:00:00

  • Diallyl disulfide (DADS) enhances gap-junctional intercellular communication by both direct and indirect mechanisms in rat liver cells.

    abstract::Diallyl disulfide (DADS), a sulfur compound from garlic has been shown to exert many biological effects: induction of carcinogen detoxication, inhibition of tumor cell proliferation, etc. These effects are consistent with its anticarcinogenic properties in animal models and could account for garlic protective effects ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg182

    authors: Huard C,Druesne N,Guyonnet D,Thomas M,Pagniez A,Le Bon AM,Martel P,Chaumontet C

    更新日期:2004-01-01 00:00:00

  • A comparative examination of the in vitro metabolism of five cyclopenta[a]phenanthrenes of varying carcinogenic potential.

    abstract::Metabolites of 15,16-dihydrocyclopenta[a]phenanthren-17-one and its 1- and 12-methyl homologues (all non-carcinogens) along with those from the 11-methyl and 11,12-dimethyl-17-ketones (carcinogens), produced in vitro by hepatic microsomes from methylcholanthrene induced rats, were separated by reverse phase h.p.l.c. I...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.8.1217

    authors: Coombs MM,Russell JC,Jones JR,Ribeiro O

    更新日期:1985-08-01 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

  • Overexpression of phosphoinositide-specific phospholipase Cgamma in NIH 3T3 cells promotes transformation and tumorigenicity.

    abstract::Phosphoinositide-specific phospholipase Cgamma (PLCgamma) is a key regulatory enzyme that binds to the phosphoryl-tyrosine residues in the cytoplasmic domain of certain activated receptors and catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] forming IP3 and diacylglycerol (DAG) in resp...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.1.177

    authors: Smith MR,Court DW,Kim HK,Park JB,Rhee SG,Rhim JS,Kung HF

    更新日期:1998-01-01 00:00:00

  • Effects on intercellular communication in human keratinocytes and liver-derived cells of polychlorinated biphenyl congeners with differing in vivo promotion activities.

    abstract::Several purified polychlorinated biphenyl (PCB) congeners with differing toxicity/tumor promotional activities in rat liver in vivo were tested for their effects on gap-junctional intercellular communication (GJIC) in cell strains and lines derived from human liver and skin. This in vitro assay is being developed to d...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.6.921

    authors: Swierenga SH,Yamasaki H,Piccoli C,Robertson L,Bourgon L,Marceau N,Fitzgerald DJ

    更新日期:1990-06-01 00:00:00