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.


: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- and O6-benzylguanine were substituted for the first, second or both the first and second guanine residues of codon 12 (GGA). DNA from isolated transformed colonies was amplified by PCR and directly sequenced by high-temperature manual and automated methods. The results show that O6-ethylguanine and O6-benzylguanine induced semi-targeted as well as targeted mutations, in contrast to O6-methylguanine, which induced only targeted mutations. When incorporated in place of the first guanine of H-ras codon 12, the targeted mutations induced by all these modified guanines were exclusively G-->A transitions. When incorporated at the second position of codon 12, O6-benzylguanine induced G-->A, G-->T and G-->C mutations. O6-Ethylguanine at the second position induced chiefly G-->A transitions, and O6-methylguanine induced G-->A transitions exclusively. Semi-targeted mutations were strictly G-->A at the base 3' to a position 1 adduct or 5' to a position 2 adduct. The mechanism for induction of targeted mutations probably involves decreasing preference to thymidine incorporation opposite an O6-modified guanine as the size of the O6-substituent increases, while the mechanism for non-targeted mutations may be related to abasic site formation or to translesion synthesis which might be made error-prone by obstructive DNA lesions in this context.






Bishop RE,Pauly GT,Moschel RC




Has Abstract


1996-04-01 00:00:00












  • A CCL2/ROS autoregulation loop is critical for cancer-associated fibroblasts-enhanced tumor growth of oral squamous cell carcinoma.

    abstract::Cancer-associated fibroblasts (CAFs) have been described to play critical roles in initiation, progression and metastasis of various cancers. However, the involvement of CAFs in oral cancer (OC) has not been well addressed. In this study, we demonstrate that CAFs, when cocultured with OC cells (OCCs), produce high lev...


    pub_type: 杂志文章


    authors: Li X,Xu Q,Wu Y,Li J,Tang D,Han L,Fan Q

    更新日期:2014-06-01 00:00:00

  • Curcumin inhibits COPD-like airway inflammation and lung cancer progression in mice.

    abstract::Recent studies have demonstrated that K-ras mutations in lung epithelial cells elicit inflammation that promotes carcinogenesis in mice (intrinsic inflammation). The finding that patients with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, have an increased risk of lung cancer after...


    pub_type: 杂志文章


    authors: Moghaddam SJ,Barta P,Mirabolfathinejad SG,Ammar-Aouchiche Z,Garza NT,Vo TT,Newman RA,Aggarwal BB,Evans CM,Tuvim MJ,Lotan R,Dickey BF

    更新日期:2009-11-01 00:00:00

  • G to A transitions and G to T transversions in codon 12 of the Ki-ras oncogene isolated from mouse lung tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and related DNA methylating and pyridyloxobutylating agents.

    abstract::Lung tumors were induced in A/J mice by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the related compounds acetoxymethylmethylnitrosamine (AMMN) and 4-acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc). NNK both methylates and pyridyloxobutylates DNA while AMMN and...


    pub_type: 杂志文章


    authors: Ronai ZA,Gradia S,Peterson LA,Hecht SS

    更新日期:1993-11-01 00:00:00

  • Dependence of u.v.-induced DNA excision repair on deoxyribonucleoside triphosphate concentrations in permeable human fibroblasts: a model for the inhibition of repair by hydroxyurea.

    abstract::We have tested the hypothesis that the inhibition by hydroxyurea of repair patch ligation and chromatin rearrangement during u.v.-induced DNA excision repair results from a reduction in cellular deoxyribonucleotide concentrations and not from a direct effect of hydroxyurea on the repair process. Using permeable human ...


    pub_type: 杂志文章


    authors: Hunting DJ,Dresler SL

    更新日期:1985-10-01 00:00:00

  • Inhibitory effect of alpha-tocopherol on the formation of nitrosomorpholine in mice treated with morpholine and exposed to nitrogen dioxide.

    abstract::The possibility that alpha-tocopherol (vitamin E) inhibits the formation of nitrosomorpholine (NMOR) in vivo was investigated in mice orally pretreated with alpha-tocopherol (2.5-100 mg/kg body wt) once daily for 6 days. Twenty-four hours later, the animals were injected i.p. with 2 mg of morpholine (MOR) per animal f...


    pub_type: 杂志文章


    authors: Norkus EP,Kuenzig WA,Chau J,Mergens WJ,Conney AH

    更新日期:1986-03-01 00:00:00

  • Purification and characterization of rat hepatic microsomal N,O-acyltransferases.

    abstract::Hepatic microsomes of female F344 rats were capable of N,O-acyltransfer of N-hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) and N-hydroxy-N-formyl-2-aminofluorene (N-OH-FAF), N-deacetylation of N-OH-AAF and N-acetyl-2-aminofluorene (2-AAF), and O-deacetylation of 4-nitrophenyl acetate (NPA). The activity for N,O-acyltran...


    pub_type: 杂志文章


    authors: Wang CY,Zukowski K,Lee MS,Sone T

    更新日期:1992-11-01 00:00:00

  • Induction of ornithine decarboxylase and DNA synthesis in rat stomach mucosa by methylglyoxal.

    abstract::Administration of methylglyoxal at doses of 300-600 mg/kg body weight by gastric tube to male F344 rats induced 100-fold increase in ornithine decarboxylase activity (formation of 682 pmol CO2/30 min/mg protein) within 7 h, 26-fold increase in DNA synthesis (incorporation of 17 800 d.p.m. of [3H]thymidine/microgram DN...


    pub_type: 杂志文章


    authors: Furihata C,Sato Y,Matsushima T,Tatematsu M

    更新日期:1985-01-01 00:00:00

  • A correlation of the rate of N-hydroxylation of aminoazo dyes with their carcinogenic activity in the rat.

    abstract::The rate of formation of N-hydroxy-N-methyl-4-aminoazobenzene (N-OH-MAB) derivatives from N,N-dimethyl-4-aminoazobenzene (DAB) derivatives and from N-methyl-4-aminoazobenzene (MAB) derivatives was measured by the e.s.r. spectroscopy, and the rate of N-demethylation of DAB derivatives was measured by h.p.l.c. The rate ...


    pub_type: 杂志文章


    authors: Kimura T,Kodama M,Nagata C

    更新日期:1982-01-01 00:00:00

  • Grb2 binding to Tyr284 in TbetaR-II is essential for mammary tumor growth and metastasis stimulated by TGF-beta.

    abstract::We demonstrated previously that growth factor receptor-bound protein 2 (Grb2) associates with the transforming growth factor-beta (TGF-beta) type II receptor [TbetaR-II] upon its phosphorylation on Tyr284 by Src. Although this phosphotransferase reaction is critical in mediating TGF-beta stimulation of epithelial-mese...


    pub_type: 杂志文章


    authors: Galliher-Beckley AJ,Schiemann WP

    更新日期:2008-02-01 00:00:00

  • DNA polymerases in replication and repair of DNA during carcinogenesis induced by feeding N-acetylaminofluorene.

    abstract::To study the roles of DNA polymerases alpha and beta during replication and repair of damaged DNA, use was made of the fact that during chronic treatment with carcinogens, replication and repair do not necessarily follow the same time sequence. Early cell damage and restorative hyperplasia cause a transient wave of DN...


    pub_type: 杂志文章


    authors: Craddock VM

    更新日期:1981-01-01 00:00:00

  • In vitro transformation of mesenchymal stem cells induces gradual genomic hypomethylation.

    abstract::Genome-wide DNA hypomethylation was one of the first epigenetic alterations described in cancer cells. However, the cause of this hypomethylation is still poorly understood. We have previously developed a line of primary mesenchymal stem cells (MSC, the putative origin of various types of sarcoma) in which five oncoge...


    pub_type: 杂志文章


    authors: Wild L,Funes JM,Boshoff C,Flanagan JM

    更新日期:2010-10-01 00:00:00

  • Okadaic acid inhibits PDGF-induced proliferation and decreases PDGF receptor number in C3H/10T1/2 mouse fibroblasts.

    abstract::Okadaic acid is both a potent inhibitor of protein serine/threonine phosphatases and a tumor promoter in the mouse skin model. We have previously shown that at non-toxic nanomolar concentrations okadaic acid reversibly inhibits induction (promotion) by PDGF of transformed cells by the 'complete' and 'two-stage' protoc...


    pub_type: 杂志文章


    authors: Dean NM,Mordan LJ,Tse K,Mooberry SL,Boynton AL

    更新日期:1991-04-01 00:00:00

  • Polymorphisms in genes involved in GH1 release and their association with breast cancer risk.

    abstract::The regulation of growth hormone 1 (GH1) and insulin-like-growth factor-1 (IGF-1) release is under the influence of three pituitary hormones [growth hormone releasing hormone (GHRH), ghrelin (GHRL) and somatostatin (SST)], which act in an autocrine/paracrine fashion in the breast. By binding to their respective recept...


    pub_type: 杂志文章


    authors: Wagner K,Hemminki K,Grzybowska E,Klaes R,Burwinkel B,Bugert P,Schmutzler RK,Wappenschmidt B,Butkiewicz D,Pamula J,Pekala W,Försti A

    更新日期:2006-09-01 00:00:00

  • Src kinase is a direct target of apigenin against UVB-induced skin inflammation.

    abstract::Apigenin, a flavonoid abundant in various vegetables and fruits, including parsley and onions, has been reported to possess anticarcinogenic effects. However, the direct molecular target of apigenin and its chemopreventive effect on ultraviolet (UV)-induced skin inflammation are not understood fully. Herein, we examin...


    pub_type: 杂志文章


    authors: Byun S,Park J,Lee E,Lim S,Yu JG,Lee SJ,Chen H,Dong Z,Lee KW,Lee HJ

    更新日期:2013-02-01 00:00:00

  • Tumor-initiating activity and carcinogenicity of dibenzo[a,l]pyrene versus 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene at low doses in mouse skin.

    abstract::Dibenzo[a,l]pyrene (DB[a,l]P) is an extremely potent carcinogen that may be present in environmental samples. Dose-response studies were conducted at low doses in mouse skin by initiation-promotion and repeated application to compare its activity to that of 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (B[a]P)...


    pub_type: 杂志文章


    authors: Higginbotham S,RamaKrishna NV,Johansson SL,Rogan EG,Cavalieri EL

    更新日期:1993-05-01 00:00:00

  • Polymorphisms in estrogen- and androgen-metabolizing genes and the risk of gastric cancer.

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    pub_type: 杂志文章


    authors: Freedman ND,Ahn J,Hou L,Lissowska J,Zatonski W,Yeager M,Chanock SJ,Chow WH,Abnet CC

    更新日期:2009-01-01 00:00:00

  • The ADAM17 protease promotes tobacco smoke carcinogen-induced lung tumorigenesis.

    abstract::Lung cancer is the leading cause of cancer-related mortality, with most cases attributed to tobacco smoking, in which nicotine-derived nitrosamine ketone (NNK) is the most potent lung carcinogen. The ADAM17 protease is responsible for the ectodomain shedding of many pro-tumorigenic cytokines, growth factors and recept...


    pub_type: 杂志文章


    authors: Saad MI,McLeod L,Yu L,Ebi H,Ruwanpura S,Sagi I,Rose-John S,Jenkins BJ

    更新日期:2020-06-17 00:00:00

  • No tumor-specific expression levels of protein kinase C isoenzymes and of c-fos in human breast cancer cell cultures.

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    pub_type: 杂志文章


    authors: Imber R,Haberthür F,Meier F,Filipuzzi I,Almendral AC

    更新日期:1994-02-01 00:00:00

  • Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak.

    abstract::Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and caspases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28 (mutan...


    pub_type: 杂志文章


    authors: Zhou XM,Wong BC,Fan XM,Zhang HB,Lin MC,Kung HF,Fan DM,Lam SK

    更新日期:2001-09-01 00:00:00

  • EGF promotes neuroendocrine-like differentiation of prostate cancer cells in the presence of LY294002 through increased ErbB2 expression independent of the phosphatidylinositol 3-kinase-AKT pathway.

    abstract::An increased neuroendocrine (NE) cell population in prostate cancer is associated with more aggressive disease and recurrence after androgen-deprivation therapy, although the mechanism responsible is unknown. In this study, we report that the treatment of LNCaP cells with epidermal growth factor (EGF) in the presence ...


    pub_type: 杂志文章


    authors: Cortés MA,Cariaga-Martinez AE,Lobo MV,Martín Orozco RM,Motiño O,Rodríguez-Ubreva FJ,Angulo J,López-Ruiz P,Colás B

    更新日期:2012-06-01 00:00:00

  • Mutagenicity of the mononitrobenzo[a]pyrenes in Chinese hamster ovary cells mediated by rat hepatocytes or liver S9.

    abstract::Previous studies have shown that 1- and 3-nitrobenzo[a]pyrene (NBaP) were mutagenic in the Salmonella reversion assay without exogenous activation and that 1-, 3- and 6-NBaP were mutagenic in the presence of hepatocytes or liver homogenate (S9). In the present study, 1-, 3- and 6-NBaP were tested for mutagenicity in C...


    pub_type: 杂志文章


    authors: Hass BS,Heflich RH,Schol HM,Chou MW,Fu PP,Casciano DA

    更新日期:1986-04-01 00:00:00

  • 32P-postlabelling/HPLC assay reveals an enantioselective adduct formation in N7 guanine residues in vivo after 1,3-butadiene inhalation exposure.

    abstract::We have established a protocol that allows qualitative and quantitative determination of butadiene monoepoxide-DNA adducts formed as a result of inhalation exposure to 1,3-butadiene. We observed that in this particular case in vivo samples required extensive sample purification to facilitate a low background. Sample p...


    pub_type: 杂志文章


    authors: Koivisto P,Sorsa M,Pacchierotti F,Peltonen K

    更新日期:1997-02-01 00:00:00

  • Compartmental analysis of the disposition of benzo[a]pyrene in rats.

    abstract::We have previously reported the disposition of benzo[a]pyrene (B[a]P) and its metabolites in male Sprague-Dawley rats following intratracheal instillation of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1986) Cancer Res., 46, 5655-5661]. In some experiments, cannulas were implanted in the bile duct of the animals prior to...


    pub_type: 杂志文章


    authors: Bevan DR,Weyand EH

    更新日期:1988-11-01 00:00:00

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

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    pub_type: 杂志文章


    authors: Rubbi CP,Milner J

    更新日期:2001-11-01 00:00:00

  • Effect of modifying agents on the phenotypic expression of cytochrome P-450, glutathione S-transferase molecular forms, microsomal epoxide hydrolase, glucose-6-phosphate dehydrogenase and gamma-glutamyltranspeptidase in rat liver preneoplastic lesions.

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    pub_type: 杂志文章


    authors: Tsuda H,Moore MA,Asamoto M,Inoue T,Ito N,Satoh K,Ichihara A,Nakamura T,Amelizad Z,Oesch F

    更新日期:1988-04-01 00:00:00

  • HGF induces CXCR4 and CXCL12-mediated tumor invasion through Ets1 and NF-kappaB.

    abstract::CXCR4 is a chemokine receptor probably involved in the homing of metastatic breast cancer, and its expression is modulated by tumor environmental stimuli such as hepatocyte growth factor (HGF) and hypoxia. Here, we demonstrate that, depending on the stimulus, different transcription factors can cooperate in enhancing ...


    pub_type: 杂志文章


    authors: Maroni P,Bendinelli P,Matteucci E,Desiderio MA

    更新日期:2007-02-01 00:00:00

  • Evidence for endogenous formation of tobacco-specific nitrosamines in rats treated with tobacco alkaloids and sodium nitrite.

    abstract::Carcinogenic tobacco-specific nitrosamines are present in tobacco products and are believed to play a significant role in human cancers associated with tobacco use. Additional amounts of tobacco-specific nitrosamines could be formed endogenously. We tested this hypothesis by treating rats with nicotine and sodium nitr...


    pub_type: 杂志文章


    authors: Carmella SG,Borukhova A,Desai D,Hecht SS

    更新日期:1997-03-01 00:00:00

  • Novel detection by magnetic microcapsules in the human gastrointestinal tract of cross-linking agents and diet-dependent reactive oxygen species.

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    pub_type: 杂志文章


    authors: Bingham SA,Ellul A,Cummings JH,O'Neill I

    更新日期:1992-04-01 00:00:00

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

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    pub_type: 杂志文章


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

    更新日期:1985-10-01 00:00:00

  • Absence of DNA breaks during repair of DNA-protein cross-links induced by the mycotoxin botryodiplodin in mammalian cells.

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    pub_type: 杂志文章


    authors: Moulé Y,Darracq N

    更新日期:1984-10-01 00:00:00