Abstract:
:Chloroethylnitrosoureas induce reactive O6-guanine adducts in DNA that can form either interstrand cross-links or a covalent complex with the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). To test our hypothesis that these end-products are formed from the common precursor, 1-O6-ethanoguanine, we compared the kinetics of interstrand cross-link formation with those of decay of MGMT complex forming capacity. The half-lives of these processes were identical. Our hypothesis also predicts that the linkage between DNA and MGMT is 1-(guan-1-yl)-2-(cystein-S-yl)ethane. This notion was tested by forming the complex with 35S-labeled recombinant human MGMT and a chloroethylnitrosourea-treated oligodeoxynucleotide. After degradation by depurination and proteolytic digestion, the identity of the [35S]cysteine-guanine linkage was confirmed by comparison with the synthetic marker compound using high performance liquid chromatography and UV spectrometry. These results strengthen the hypothesis that DNA interstrand cross-links and DNA-MGMT complex both arise from the same precursor. The data also suggest that 1-O6-ethanoguanine is a good substrate for MGMT such that, under certain conditions in vivo, DNA-MGMT complex formation may constitute a significant secondary lesion.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Gonzaga PE,Potter PM,Niu TQ,Yu D,Ludlum DB,Rafferty JA,Margison GP,Brent TPsubject
Has Abstractpub_date
1992-11-01 00:00:00pages
6052-8issue
21eissn
0008-5472issn
1538-7445journal_volume
52pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Using Mth1 and Ogg1 knockout mice, we evaluated the roles of these enzymes to prevent tumorigenesis and the accumulation of 8-oxoguanine (8-oxoG) in DNA. We found that lung adenoma/carcinoma spontaneously developed in Ogg1 knockout mice approximately 1.5 years after birth in which 8-oxoG was found to accumulate in the...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
abstract::Metastatic cases of breast cancer pose the primary challenge in clinical management of this disease, demanding the identification of effective therapeutic strategies that remain wanting. In this study, we report that elevated levels of α-tubulin acetylation are a sufficient cause of metastatic potential in breast canc...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-3563
更新日期:2015-01-01 00:00:00
abstract::Earlier studies have shown guanine arabinoside (ara-G) is an effective agent against growth of T-cell lines and freshly isolated human T-leukemic cells. However, poor water solubility of ara-G limits clinical use. 2-Amino-6-methoxypurine arabinoside (506U) is a water-soluble prodrug converted to ara-G by adenosine dea...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Photoimmunotherapy (using a monoclonal antibody-targeted photosensitizer and red light) may be a strategy to overcome the limitations inherent in photodynamic therapy of liver tumors. The aims of this study were (a) to test the efficacy of selective treatment of hepatic metastases of colorectal cancer in an orthotopic...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-08-01 00:00:00
abstract::To elucidate the role of the recently identified FHIT gene, located at 3p14.2 in human brain tumor carcinogenesis, a total of 259 tumors were analyzed for loss of heterozygosity (LOH) at microsatellite loci D3S1313, D3S1234, D3S1300, and D3S1481. In primary brain tumors, LOH was detected at a frequency of 8.4% (n = 21...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::Of 20,000 plant extracts submitted to the National Cancer Institute antitumor screens from 1960 to 1980, over 95% exhibited inadequate tumor-inhibiting activity or promoted tumor growth. Of these, 50 extracts representing 42 species showed significant levels of tumor growth enhancement compared to controls on the basi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-12-01 00:00:00
abstract::The tumorigenic activity of a series of N-methyl-N'-aryl-N-nitrosoureas (I-X) on mouse skin was investigated in comparison with that of N-methyl-N-nitrosourea (MNU). The tumorigenic potency of I-X was less than that of MNU, although the former are much stronger mutagens; and no correlations were found between the tumo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract::PTEN/MMAC1 is a major new tumor suppressor gene that encodes a dual-specificity phosphatase with sequence similarity to the cytoskeletal protein tensin. Recently, we reported that PTEN dephosphorylates focal adhesion kinase (FAK) and inhibits cell migration, spreading, and focal adhesion formation. Here, the effects o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-01-15 00:00:00
abstract::Emerging technologies allow broad profiling of the cancer genome for differential DNA methylation relative to benign cells. Herein, bisulfite-modified DNA from lymph nodes with either reactive hyperplasia or follicular lymphoma (FL) were analyzed using a commercial C/UpG genotyping assay. Two hundred fifty-nine differ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-2984
更新日期:2009-02-01 00:00:00
abstract::ERBB4/HER4 (referred to here as ERBB4) is a unique member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. In contrast to the other three members of the EGFR family (i.e., EGFR, ERBB2/HER2/NEU, and ERBB3), which are associated with aggressive forms of human cancers, ERBB4 expression ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2368
更新日期:2006-06-15 00:00:00
abstract::This study investigated the effect of recombinant human tumor necrosis factor (rhTNF) on hydroxyl radical production by established cell lines in vitro, and its implication in the killing of tumor cells by rhTNF. During incubation of TNF sensitive mouse tumorigenic fibroblast L-M cells (2 X 10(7) cells) in the presenc...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::We analyzed the mRNA expression of the FHIT gene by reverse transcription-PCR (RT-PCR) in 54 cases of acute lymphoblastic leukemia (ALL; 11 cases of T-cell ALL [T-ALL] and 43 cases of non-T-ALL) and 40 cases of acute myeloid leukemia (AML). In 46% of the ALL cases and 55% of the AML cases, FHIT expression was absent o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-11-15 00:00:00
abstract::An immunosuppressive peptide fraction was isolated by means of gel filtration, membrane partition, and ion-exchange chromatography from the sera of patients hospitalized for cancer. The resulting peptide fraction, which was heterogeneous as judged by high-voltage electrophoresis, was found to suppress both phytohemagg...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-06-01 00:00:00
abstract::Alterations in expression of or responsiveness to transforming growth factor beta (TGF-beta) are frequently found in human and animal epithelial cancers and are though to be important for loss of growth control in the neoplastic cell. We show here that keratinocyte cell lines from mice with a targeted deletion of the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-08-15 00:00:00
abstract::Epidemiological and animal studies (reviewed in Y. I. Kim, J. Nutr. Biochemistry, 10: 66-88, 1999; J. B. Mason and T. Levesque, Oncology, 10: 1727-1743, 1996) suggest that dietary folate intake is inversely related to the risk of colorectal cancer. However, the optimal timing of folate intervention and mechanisms by w...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-06-15 00:00:00
abstract::The genetic status of cyclin genes was examined in a panel of 47 colorectal carcinoma cell lines. Cyclin D2 was found to be amplified in one tumor and cyclin E in another. In each of the two cases, the amplified cyclin gene was overexpressed at the protein or mRNA level. Cyclin D1, previously shown to be amplified in ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::cis-Platinum, bleomycin, 5-fluorouracil, and cyclophosphamide were administered to rodent and canine models of osmotic blood-brain barrier modification to evaluate the relationship between tissue drug concentration in brain and the physiological and neuropathological effects of the drug. The toxicity studies were carr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-11-01 00:00:00
abstract::The epidermal growth factor (EGF) receptor in two colon carcinoma lines and in one vulval carcinoma line tested contains carbohydrate determinants that are recognized by monoclonal antibodies to tumor-associated antigens. These antibodies are directed to sialylated Lea and to difucosylated structures of the Y type. Ce...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-05-15 00:00:00
abstract::To understand the involvement of allelic losses and inactivation of tumor suppressor genes for the development of endometrial carcinoma of the uterus (EC), 24 cases of EC were examined for loss of heterozygosity (LOH) using a total of 57 polymorphic DNA markers covering all 23 pairs of chromosomes. LOH was observed at...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::The nucleotide metabolism enzyme ribonucleotide reductase is composed of a regulatory subunit (RRM1) and a catalytic subunit (RRM2). The RRM1 locus has frequent loss of heterozygosity in lung cancers, ectopic expression of RRM1 suppresses proliferation of ras-transformed mouse fibroblasts, and high levels of RRM1 expr...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-4462
更新日期:2006-07-01 00:00:00
abstract::Here, we report the molecular regulation of interleukin (IL)-8 expression in human melanoma cells. The inflammatory cytokines IL-1beta and tumor necrosis factor-alpha (TNF-alpha) up-regulated IL-8 expression, in a time- and concentration-dependent manner, in three metastatic melanoma variants, SBC-2 (nonmetastatic), A...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-04-01 00:00:00
abstract::4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is activated to DNA alkylating species via two different alpha-hydroxylation pathways. Methylene hydroxylation leads to DNA methylation, whereas methyl hydroxylation yields DNA pyridyloxobutylation. We have developed a high-pressure liquid chromatography assay utili...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::Methylation associated inactivation of RASSF1, a putative tumor suppressor identified at 3p21.3, has been frequently observed in several human malignancies, including lung and breast cancers. To explore the penetrance of RASSF1 in gastric carcinogenesis, we performed expression and mutation analyses of 3 isotypes of R...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::Cytogenetic study of short-term cultures from 10 adipose tissue tumors (eight lipomas, one myxoid liposarcoma, and one mixed liposarcoma) have revealed clonal chromosome abnormalities in seven cases. In both malignant tumors, translocation (12;16) was the sole aberration, and in the mixed liposarcoma, the breakpoints ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::We used three techniques to examine excision repair in human cells treated with ultraviolet radiation, N-acetoxy-2-acetylaminofluorene, and a combination of the two. The three techniques gave similar results. Two types of human cells were used: (a) excision repair proficient (normal human fibroblasts and xeroderma pig...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::The interaction of the activating receptor NKG2D with its ligands plays an important role in immunosurveillance of tumors and infectious pathogens, but dysregulation of this system may lead to autoimmunity. The expression of NKG2D ligands is induced by cellular "stress." However, the regulation of expression of these ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2973
更新日期:2008-03-01 00:00:00
abstract::Liver X receptors function as central transcriptional regulators for lipid homeostasis, for which agonists have been developed as potential drugs for treatment of cardiovascular diseases and metabolic syndromes. Because dysregulation of lipid metabolism has been implicated in sex hormone-dependent cancers, we investig...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-2332
更新日期:2004-11-01 00:00:00
abstract::3-(Iodoacetamido)-benzoylurea (3-IAABU) is a newly synthesized antitubulin compound with a molecular weight of 347. 3-IAABU exhibited anticancer activity in a variety of tumor cell lines with ID90 in the range of 0.015-0.29 microM for leukemic cells and 0.06-0.92 microM for solid tumors. Higher selectivity against mal...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::The tumorigenicity of dexamethasone-treated tissue-cultured mammary tumor cells was compared to that of untreated mammary tumor cells. The dexamethasone-induced cells progressed faster in normal syngeneic animals than did untreated mammary tumor cells. The fact that the growth rate differential was also observed in at...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-10-01 00:00:00
abstract::The mammary carcinoma cell line MFM-223 is characterized by high androgen and low estrogen and progesterone receptor levels. With the dextran charcoal method, androgen binding was determined at 160 fmol/mg protein corresponding to approximately 100,000 binding sites per cell in whole cell binding assays. The estrogen ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00