Abstract：
:Exposure of HeLa cells to 0.2 mM O6-methylguanine for 4 h or longer led to a 70-80% loss in the activity of the DNA-repair protein, O6-alkylguanine-DNA alkyltransferase. The decline in alkyltransferase activity brought about by O6-methylguanine was reversible on removing the base but at least 48 h were required for complete restoration. This loss of activity could also be brought about by other O6-alkylguanines including ethyl, n-propyl, and n-butyl, but the isopropyl and 2-hydroxyethyl derivatives were considerably less active. The rate of decline of alkyltransferase activity produced by O6-methylguanine was much more rapid than the rate of loss when protein synthesis was inhibited indicating that it was not brought about by blocking the synthesis of the protein. The loss of alkyltransferase activity was not prevented by the addition of inhibitors of nucleic acid or protein synthesis suggesting that it did not require protein synthesis or the incorporation of the O6-alkylguanine into nucleic acids. When cell free O6-alkylguanine-DNA alkyltransferase preparations were incubated in vitro with O6-methylguanine they became inactivated and when O6-[3H]methylguanine was used, [3H]guanine was produced. The inactivation was concentration dependent requiring 0.4 mM for a maximal rate and was quite slow requiring 3-4 hours for completion. These results suggest that the loss of O6-alkylguanine-DNA alkyltransferase activity is brought about by the free base acting as a very weak substrate for the protein. Exposure of mammalian cells to O6-methylguanine or O6-n-butylguanine provides a means by which the level of O6-alkylguanine-DNA-alkyltransferase can be regulated experimentally. This should enable the design of experiments to examine the role of O6-alkylguanine adducts in mutagenesis, carcinogenesis, and cell toxicity after administration of alkylating agents.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Dolan ME,Morimoto K,Pegg AEsubject
Has Abstractpub_date
1985-12-01 00:00:00pages
6413-7issue
12 Pt 1eissn
0008-5472issn
1538-7445journal_volume
45pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Cytogenetic analysis of tumor cells from a human malignant melanoma was performed on both the primary tumor colony-forming cells and a cell line (HA-A) established subsequently from the clonogenic population. Chromosome-banding analysis demonstrated identical karyotypic alterations in both the tumor colony-forming cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:TEL-AML1 gene fusion derived by chromosomal translocation is a common acquired genetic lesion in pediatric cancer that is present in approximately 25% of B-cell precursor acute lymphoblastic leukemias, and recent evidence suggests that this recombination event may initiate leukemogenesis prenatally during fetal hemopo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-08-15 00:00:00
abstract：:Class I major histocompatibility complex (MHC) antigen expression in neuroblastoma may play a role in the oncogenicity of this embryonal tumor of childhood. Since N-myc amplification in neuroblastoma tumors is associated with rapid tumor progression (33) and N-myc decreases Class I MHC antigen expression in rat neurob...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-06-15 00:00:00
abstract：:The increasing availability and maturity of DNA microarray technology has led to an explosion of cancer profiling studies. To extract maximum value from the accumulating mass of publicly available cancer gene expression data, methods are needed to evaluate, integrate, and intervalidate multiple datasets. Here we demon...
journal_title：Cancer research
pub_type： 杂志文章,meta分析
doi：
更新日期：2002-08-01 00:00:00
abstract：:Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as a major source of therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galect...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-3013
更新日期：2014-07-01 00:00:00
abstract：:Tetracyclines, a class of antibiotics that target bacterial translation, are commonly used in research for inducible gene expression using Tet-ON/Tet-OFF systems. However, such tetracycline-inducible systems carry a risk. Given that mitochondria have a "bacterial" ancestry, these antibiotics also target mitochondrial ...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-15-1626
更新日期：2015-11-01 00:00:00
abstract：:The discovery of somatic mutations in EGFR and development of EGFR tyrosine kinase inhibitors (TKI) have revolutionized treatment for lung cancer. However, resistance to TKIs emerges in almost all patients and currently no effective treatment is available. Here, we show that β-catenin is essential for development of E...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-0184
更新日期：2014-10-15 00:00:00
abstract：:Despite strong evidence of an association between Helicobacter pylori and gastric cancer, the benefit of eradicating H. pylori infection is unknown. Our aim was to test the hypothesis that exposure to high doses of antibiotics reduces risk for gastric cancer via possible eradication of H. pylori We conducted a nationw...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-11-15 00:00:00
abstract：:The adoptive transfer of recombinant-methionyl human interleukin 2 (rIL-2)-activated autologous peripheral blood mononuclear lymphokine-activated killer (LAK) cells to cancer patients is being evaluated as an alternative to conventional cancer therapy. We have independently developed an alternative regimen to previous...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
abstract：:The product of the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor gene, menin, is an integral component of MLL1/MLL2 histone methyltransferase complexes specific for Lys4 of histone H3 (H3K4). We show that menin is a transcriptional coactivator of the nuclear receptors for estrogen and vitamin D. Activati...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-4461
更新日期：2006-05-01 00:00:00
abstract：:Autologous hematopoietic stem cell transplantation after myelosuppressive chemotherapy is used for the treatment of high-risk breast cancer and other solid tumors. However, contamination of the autologous graft with tumor cells may adversely affect outcomes. Human hematopoietic bone marrow cells are resistant to herpe...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, r...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
abstract：:The production of CD73-derived adenosine (Ado) by Tregs has been proposed as a resistance mechanism to anti-PD-1 therapy in murine tumor models. We reported that human Tregs express the ectonucleotidase CD39, which generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effect...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-2405
更新日期：2018-07-01 00:00:00
abstract：:The influences of pure human pluripotent colony-stimulating factor, highly purified pluripoietin alpha, pure recombinant human tumor necrosis factor alpha, pure recombinant human gamma-interferon, and natural prostaglandin E1 (PGE1) were evaluated on colony formation of multipotential and erythroid progenitor cells in...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:Heparanase is overexpressed in many solid tumor cells and is capable of specifically cleaving heparan sulfate, and this activity is associated with the metastatic potential of tumor cells; however, the activation mechanism of heparanase has remained unknown. In this study, we investigated the link between disulfide bo...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-1053
更新日期：2007-08-15 00:00:00
abstract：:Male Sprague-Dawley rats were given weekly s.c. injections of 1,2-dimethylhydrazine (21 mg/kg) for 20 weeks. The injections were then discontinued, and, after an interval of 2 to 8 weeks, experimental animals were given i.p. injections of 5,6-dihydroxytryptamine (5,6DHT) at a dose of 40 mg/kg and sacrificed at interva...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-04-01 00:00:00
abstract：:The multistage process of cancer formation is driven by the progressive acquisition of somatic mutations. Replication stress creates genomic instability in mammals. Using a well-defined multistep leukemia model driven by Spi-1/PU.1 overexpression in the mouse and Spi-1/PU.1-overexpressing human leukemic cells, we inve...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-4691
更新日期：2010-09-01 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：:Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most used drugs for osteosarcoma chemotherapy. By using a series of CDDP-resistant variants, which were established from the U-2OS and Saos-2 human osteosarcoma cell lines, we found that CDDP resistance was mainly associated with the increase of both the int...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-5840
更新日期：2008-08-15 00:00:00
abstract：:2-Amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine present in pyrolysate products of meat and fish and has been shown to induce tumors in the colon, mammary gland, and possibly lymphatic system. Experiments were designed to examine the lymphoma-inducing capacity o...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:Using alternative reading frames, the human ARF-INK4a locus encodes two unrelated proteins that both function in tumor suppression. p16(INK4a) maintains the retinoblastoma protein in its growth-suppressive state through inhibition of cyclin D-dependent kinase activity, whereas ARF binds with MDM2 and stabilizes p53. T...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-02-15 00:00:00
abstract：:Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passag...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-3142
更新日期：2017-02-15 00:00:00
abstract：:Previous studies have shown dose-dependent growth inhibition of the human mammary carcinoma cell line MDA-MB-231 xenotransplanted in athymic mice using retinol. In this study, the growth inhibitory effect of retinoic acid (RA) and 13-cis-retinoic acid (13-cis-RA) was examined in vitro and in vivo. With both agents the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-07-01 00:00:00
abstract：:Immunohistochemical localization of estrogen receptor (ER) using specific monoclonal anti-human estrogen receptor antibody, H222, with an immunoperoxidase technique was performed on fresh frozen tissue derived from 100 endometrial adenocarcinomas. Immunohistochemical evaluation incorporated both intensity and distribu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:Malignant ascites is a common complication in the late stages of epithelial ovarian cancer (EOC) that greatly diminishes the quality of life of patients. Malignant ascites is a known consequence of vascular dysfunction, but current approved treatments are not effective in preventing fluid accumulation. In this study, ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-3373
更新日期：2015-11-15 00:00:00
abstract：:The proliferation rate of HT29 colon carcinoma cells was decreased by the multitargeted antifolate (MTA), LY231514. This effect correlated with a buildup of cells near the G1-S interface after 24 h of incubation, and a synchronized progression of the population through S phase during the next 24 h. MTA treatment (0.03...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-08-01 00:00:00
abstract：:The efficacy of intracavitary chemoimmunotoxin therapy for cancer treatment was evaluated using the human colon carcinoma (HT-29) which had been xenografted i.p. into nude mice. Mice bearing HT-29 were treated with an immunotoxin consisting of the monoclonal antibody OVB3 coupled to Pseudomonas exotoxin (OVB3-PE), wit...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:The antiestrogen tamoxifen is used in the treatment of breast cancer and has recently been recommended as a chemopreventive drug for women at high risk for breast cancer. However, women treated with the drug have an increased incidence of endometrial cancer. It has been suggested that this endometrial cancer might res...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-05-15 00:00:00
abstract：:Normal and transformed rat liver epithelial cell lines exhibited differences in the ability to survive in the aggregate form. Normal rat liver epithelial cells in the aggregate form underwent a rapid decline in the number of viable cells, while counterpart transformed epithelial cells exhibited an ability to survive a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-06-01 00:00:00
abstract：:We previously showed that introduction of a normal, neomycin-tagged human chromosome 11 reduces the metastatic capacity of MDA-MB-435 (435) human breast carcinoma cells by 70-90% without affecting tumorigenicity, suggesting the presence of one or more metastasis suppressor genes encoded on human chromosome 11. To iden...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
