Morphology and morphometric investigation of hepatocellular preneoplastic lesions and neoplasms in connexin32-deficient mice.


:Gap junctions are composed of protein subunits, called connexins, and provide a pathway for the exchange of ions and small molecules between contacting cells. This transfer of molecules is thought to be an important pathway for direct cell communication, and is involved in tissue homeostasis, growth control and embryonic development. Impairment of gap junctional intercellular communication (GJIC) via different mechanisms may therefore contribute to dysregulated cellular proliferation and subsequent tumor development. We investigated the effect of Connexin32-deficiency on liver histology and the formation of preneoplastic foci and hepatocellular neoplasms in transgenic knockout mice, as Connexin32 (Cx32) is the major gap junction protein in the liver. Loss of Cx32 does not alter the morphology of extrafocal liver tissue. However, after administration of a single dose of diethylnitrosamine (DEN), given 2 weeks after birth, the number and volume fraction of preneoplastic foci showed a 3.3-fold to 12.8-fold increase in the Cx32-deficient mice as compared with the corresponding wildtype groups, regardless of sex and age of the animals. Number and volume fraction of hepatocellular adenomas and carcinomas also increased significantly in these animals. The experimental groups did not differ in the morphology of the different types of preneoplastic foci and neoplasms. On the other hand, Cx32-deficiency without DEN treatment did not lead to an increase in the spontaneous development of any type of preneoplastic hepatic foci or hepatocellular neoplasms in up to 18-month-old Cx32-deficient mice as compared with wildtype controls. In conclusion, our results indicate that impairment of GJIC in mouse liver due to deletion of the Cx32 coding DNA clearly promotes the carcinogenic effect of DEN administration and results in a higher susceptibility to hepatocellular neoplasms, but does not appear to initiate hepatic tumor development.






Evert M,Ott T,Temme A,Willecke K,Dombrowski F





Has Abstract


2002-05-01 00:00:00












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    abstract::The haloethylnitrosoureas form a cytotoxic DNA cross-link in a series of reactions which involves initial alkylation of the O6 position of guanine and rearrangement to the intermediate, 1,O6-ethanoguanine; 1,O6-ethanoguanine then reacts with a neighboring cytosine base. O6-Alkylguanine-DNA alkyltransferase can interru...


    pub_type: 杂志文章


    authors: Niu T,Yu D,Kirk MC,Ludlum DB

    更新日期:1993-02-01 00:00:00

  • AFF4 promotes tumorigenesis and tumor-initiation capacity of head and neck squamous cell carcinoma cells by regulating SOX2.

    abstract::Super elongation complex (SEC) controls gene transcription by releasing Pol II from pausing. Previous studies have shown that dysfunction of SEC was associated with multiple human cancers, such as leukemia and breast cancer. However, the role of SEC in head and neck squamous cell carcinoma (HNSCC) development remains ...


    pub_type: 杂志文章


    authors: Deng P,Wang J,Zhang X,Wu X,Ji N,Li J,Zhou M,Jiang L,Zeng X,Chen Q

    更新日期:2018-07-03 00:00:00

  • Neoplastic transformation of osteogenic cells: quantitative morphometric analysis of an in vitro model for osteosarcoma.

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    pub_type: 杂志文章


    authors: Birek C,Pawson T,McCulloch CA,Tenenbaum HC

    更新日期:1988-10-01 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...


    pub_type: 杂志文章


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

    更新日期:1987-10-01 00:00:00

  • CEBPG regulates ERCC5/XPG expression in human bronchial epithelial cells and this regulation is modified by E2F1/YY1 interactions.

    abstract::Marked inter-individual variation in lung cancer risk cannot be accounted for solely by cigarette smoke and other environmental exposures. Evidence suggests that variation in bronchial epithelial cell expression of key DNA repair genes plays a role. Variation in these genes correlates with variation in expression of C...


    pub_type: 杂志文章


    authors: Crawford EL,Blomquist T,Mullins DN,Yoon Y,Hernandez DR,Al-Bagdhadi M,Ruiz J,Hammersley J,Willey JC

    更新日期:2007-12-01 00:00:00

  • miR-9 targets CXCR4 and functions as a potential tumor suppressor in nasopharyngeal carcinoma.

    abstract::MicroRNA deregulation and pathway alterations have been implicated in nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer widely prevalent in Southern China. In this study, we report that miR-9 is commonly downregulated in NPC specimens and NPC cell lines with important functional consequences. The...


    pub_type: 杂志文章


    authors: Lu J,Luo H,Liu X,Peng Y,Zhang B,Wang L,Xu X,Peng X,Li G,Tian W,He ML,Kung H,Li XP

    更新日期:2014-03-01 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...


    pub_type: 杂志文章


    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

  • Transplacental genotoxicity of diethylstilbestrol.

    abstract::Diethylstilbestrol (DES) is a transplacental carcinogen in humans and in rodents. As part of an attempt to examine the mechanism of transplacental carcinogenesis, the transplacental genotoxity of this stilbene estrogen has been investigated. Pregnant hamsters received single injections of 200 mg/kg DES on the 10th day...


    pub_type: 杂志文章


    authors: Gladek A,Liehr JG

    更新日期:1991-05-01 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...


    pub_type: 杂志文章


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

    更新日期:1991-02-01 00:00:00

  • Alkenyl group is responsible for the disruption of microtubule network formation in human colon cancer cell line HT-29 cells.

    abstract::Alk(en)yl trisulfides (R-SSS-R') are organosulfur compounds produced by crushed garlic and other Allium vegetables. We found that these compounds exhibit potent anticancer effects through the reaction with microtubules, causing cell cycle arrest. Nine alk(en)yl trisulfides including dimethyl trisulfide, diethyl trisul...


    pub_type: 杂志文章


    authors: Hosono T,Hosono-Fukao T,Inada K,Tanaka R,Yamada H,Iitsuka Y,Seki T,Hasegawa I,Ariga T

    更新日期:2008-07-01 00:00:00

  • Effects of dietary indoles and isothiocyanates on N-nitrosodimethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone alpha-hydroxylation and DNA methylation in rat liver.

    abstract::Dietary-related indoles, isothiocyanates, and the allyl isothiocyanate glucosinolate, sinigrin, were administered to F344 rats in the diet for 2 weeks (chronic protocol) or by gavage 2 h before sacrifice (acute protocol) and the effects of these pretreatments on the alpha-hydroxylation of two carcinogenic nitrosamines...


    pub_type: 杂志文章


    authors: Chung FL,Wang MY,Hecht SS

    更新日期:1985-04-01 00:00:00

  • Cell specificity of rat cytokeratin p39 during azo dye-induced hepatocarcinogenesis.

    abstract::Monoclonal or affinity-purified antibodies specific to Novikoff hepatoma cytokeratin p39 were employed to study the origin and fate of p39-containing cell types during hepatocarcinogenesis induced with N,N-dimethyl-p(m-tolylazo)aniline. Frozen sections were obtained from the livers of animals autopsied temporally duri...


    pub_type: 杂志文章


    authors: Schmidt WN,Page DL,McKusick K,Hnilica LS

    更新日期:1985-08-01 00:00:00

  • Reactive oxygen species regulate insulin-induced VEGF and HIF-1alpha expression through the activation of p70S6K1 in human prostate cancer cells.

    abstract::Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) are important regulators of angiogenesis. HIF-1 is composed of HIF-1alpha and HIF-1beta subunits, and regulates VEGF expression at transcriptional level. In this study, we demonstrated that insulin induced H2O2 production and p70S6K1 acti...


    pub_type: 杂志文章


    authors: Zhou Q,Liu LZ,Fu B,Hu X,Shi X,Fang J,Jiang BH

    更新日期:2007-01-01 00:00:00

  • Impaired DNA double-strand break repair contributes to chemoresistance in HIF-1 alpha-deficient mouse embryonic fibroblasts.

    abstract::A mismatch between metabolic demand and oxygen delivery leads to microenvironmental changes in solid tumors. The resulting tumor hypoxia is associated with malignant progression, therapy resistance and poor prognosis. However, the molecular mechanisms underlying therapy resistance in hypoxic tumors are not fully under...


    pub_type: 杂志文章


    authors: Wirthner R,Wrann S,Balamurugan K,Wenger RH,Stiehl DP

    更新日期:2008-12-01 00:00:00

  • Differential flora in the microenvironment of lung tumor and paired adjacent normal tissues.

    abstract::Recent evidence demonstrates the existence of diversified microbiota in the lung. However, the effect of lung carcinogenesis on the flora in lung microenvironment has yet not been well investigated. In this study, we surveyed the microbial composition and diversity in lung tumor and paired adjacent normal tissues obta...


    pub_type: 杂志文章


    authors: Mao Q,Ma W,Wang Z,Liang Y,Zhang T,Yang Y,Xia W,Jiang F,Hu J,Xu L

    更新日期:2020-08-12 00:00:00

  • The contribution of alternative polyadenylation to the cancer phenotype.

    abstract::Eukaryotic 3'-end formation is a critical step for mRNA maturation and involves a requisite cleavage and polyadenylation event downstream of a polyadenylation signal. Recent discoveries suggest that in nearly 70% of human genes, cleavage and polyadenylation can occur at multiple locations through a process known as al...


    pub_type: 杂志文章,评审


    authors: Masamha CP,Wagner EJ

    更新日期:2018-01-12 00:00:00

  • Synthesis of 2-azido-3-methylimidazo[4,5-f]quinoline and photolytic generation of a highly reactive and mutagenic IQ derivative.

    abstract::Azido-IQ (2-azido-3-methylimidazo[4,5-f]quinoline), a novel analog of the food mutagen and carcinogen IQ (2-amino-3-methylimidazo[4,5-f]quinoline) was synthesized and characterized. Both thermolysis and photolysis of this azide yield a short-lived nitrene which can react as an electrophile either directly or via proto...


    pub_type: 杂志文章


    authors: Wild D,Dirr A

    更新日期:1988-05-01 00:00:00

  • Identification and quantitation of DNA adducts from calf thymus DNA exposed to 3,4-epoxy-1-butene.

    abstract::3,4-Epoxy-1-butene (EB) is the major mutagenic metabolite of butadiene (BD), an important industrial chemical classified as a probable human carcinogen. Although the mechanism of carcinogenicity of EB is not known, its reactions with nucleophilic sites of DNA giving pro-mutagenic lesions are likely to constitute the e...


    pub_type: 杂志文章


    authors: Tretyakova N,Lin Y,Sangaiah R,Upton PB,Swenberg JA

    更新日期:1997-01-01 00:00:00

  • DNA damage and repair in normal, xeroderma pigmentosum and XP revertant cells analyzed by gel electrophoresis: excision of cyclobutane dimers from the whole genome is not necessary for cell survival.

    abstract::Human fibroblasts were embedded in microscopic-sized agarose beads and lysed in situ to produce chromosome-sized DNA trapped inside the beads. Conventional alkaline agarose gel electrophoresis of trapped DNA from cells damaged by X-rays before embedding gave mol. wts similar to those obtained with alkaline sucrose gra...


    pub_type: 杂志文章


    authors: Cleaver JE

    更新日期:1989-09-01 00:00:00

  • Solid-phase synthesis of oligodeoxynucleotides containing O6-alkylguanine.

    abstract::Practical methods for the routine solid-phase synthesis of oligodeoxynucleotides containing O6-alkylguanine are described. It is shown that if the 2-amino group of the alkylated base is protected with a phenylacetyl group, and a mixture of nitrobenzaldoximate ions and ammonia used to remove the protecting groups from ...


    pub_type: 杂志文章


    authors: Smith CA,Xu YZ,Swann PF

    更新日期:1990-05-01 00:00:00

  • Modulation of growth and cell turnover of preneoplastic lesions and of prostaglandin levels in rat pancreas by dietary fish oil.

    abstract::In the present study the modulating effects of dietary fish oil (MaxEPA) on unsaturated fat-promoted pancreatic carcinogenesis in azaserine-treated rats were investigated. Three groups of 20 rats (each group comprised five saline-treated and 15 azaserine-treated animals) were fed an AIN76-based purified diet containin...


    pub_type: 杂志文章


    authors: Appel MJ,Woutersen RA

    更新日期:1994-10-01 00:00:00

  • Apoptosis by dietary factors: the suicide solution for delaying cancer growth.

    abstract::Apoptosis, a form of programmed cell death, plays a fundamental role in the maintenance of tissues and organ systems by providing a controlled cell deletion to balanced cell proliferation. The last decade has witnessed an exponential increase in the number of studies investigating how different components of the diet ...


    pub_type: 杂志文章,评审


    authors: Khan N,Afaq F,Mukhtar H

    更新日期:2007-02-01 00:00:00

  • Sodium taurocholate inhibits intestinal adenoma formation in APCMin/+ mice, potentially through activation of the farnesoid X receptor.

    abstract::In light of clinical and biological evidence that bile constituents exert preventive effects against colorectal cancer, we evaluated the influence of oral bilirubin and sodium taurocholate (NaTC) on intestinal tumor formation in APC(Min/+) mice. Mice received bilirubin and/or bovine serum albumin (BSA) and NaTC in the...


    pub_type: 杂志文章


    authors: Smith DL,Keshavan P,Avissar U,Ahmed K,Zucker SD

    更新日期:2010-06-01 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...


    pub_type: 杂志文章,评审


    authors: Yokota J

    更新日期:2000-03-01 00:00:00

  • The metastasis suppressor, NDRG1, attenuates oncogenic TGF-β and NF-κB signaling to enhance membrane E-cadherin expression in pancreatic cancer cells.

    abstract::The metastasis suppressor, N-myc downstream-regulated gene-1 (NDRG1), plays multifaceted roles in inhibiting oncogenic signaling and can suppress the epithelial mesenchymal transition (EMT), a key step in metastasis. In this investigation, NDRG1 inhibited the oncogenic effects of transforming growth factor-β (TGF-β) i...


    pub_type: 杂志文章


    authors: Menezes SV,Fouani L,Huang MLH,Geleta B,Maleki S,Richardson A,Richardson DR,Kovacevic Z

    更新日期:2019-07-06 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...


    pub_type: 杂志文章


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

    更新日期:1992-11-01 00:00:00

  • Induction of apoptosis in the lung but not in the liver of rats receiving intra-tracheal instillations of chromium(VI).

    abstract::Several studies have shown that hexavalent chromium [Cr(VI)] induces apoptosis in a variety of in vitro test systems. We instilled intra-tracheally either saline or sodium dichromate (0.25 mg/kg body weight), for three consecutive days, to Sprague-Dawley rats. TUNEL analyses showed a marked increase of the apoptotic i...


    pub_type: 杂志文章


    authors: D'Agostini F,Izzotti A,Bennicelli C,Camoirano A,Tampa E,De Flora S

    更新日期:2002-04-01 00:00:00

  • Evidence that weak promotion of carcinogen-initiated cells prevents their progression to malignancy.

    abstract::Repeated promotion of 7,12-dimethylbenz[alpha]anthracene-initiated cells in mouse skin with 12-O-tetradecanoylphorbol-13-acetate (TPA) induces them to grow as premalignant skin papillomas and some of these subsequently progress to carcinomas. In this study, we demonstrate that this TPA-induced progression of initiated...


    pub_type: 杂志文章


    authors: Reddy AL,Fialkow PJ

    更新日期:1990-12-01 00:00:00

  • No allelic loss at the p53 locus in 1,2-dimethylhydrazine-induced mouse colon tumours: PCR-SSCP analysis with sequence-tagged microsatellite site primers.

    abstract::We examined allelic loss in colon tumors induced by 1,2-dimethylhydrazine (DMH) in F1 hybrid mice, using sequence-tagged microsatellite site (STMS) primers derived from the chromosomal region closely linked to the p53 locus. Polymerase chain reaction--single-strand conformation polymorphism (PCR-SSCP) analysis of 155 ...


    pub_type: 杂志文章


    authors: Okamoto M,Ohtsu H,Miyaki M,Yonekawa H

    更新日期:1993-07-01 00:00:00

  • Inhibition of 7,12-dimethylbenz[a]anthracene-induced genotoxicity in Chinese hamster ovary cells by retinol and retinoic acid.

    abstract::The effects of retinol and retinoic acid on cytotoxicity and mutation expression at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary (CHO) cells with or without exogenous metabolic activation were studied in the presence and absence of known chemical mutagens. Neither retinol ...


    pub_type: 杂志文章


    authors: Budroe JD,Schol HM,Shaddock JG,Casciano DA

    更新日期:1988-07-01 00:00:00