1,721,051 research outputs found
Role of mismatch repair in the induction of chromosomal aberrations and sister chromatid exchanges in cells treated with different chemotherapeutic agents
No full textThe mismatch repair (MMR) system plays a major role in mediating the cytotoxicity and clastogenicity of agents generating O(6)-methylguanine in DNA. Loss of MMR has also been associated with tumor cell resistance to the cytotoxic effects of 6-thioguanine and cisplatin and with hypersensitivity to N-(2-chloroethyl)- N'-cyclohexyl- N-nitrosourea (CCNU). The aim of the present investigation was to elucidate the role played by the MMR system in the generation of chromosomal damage in cells exposed to 6-thioguanine, cisplatin or CCNU
Role of mismatch repair in the induction of chromosomal aberrations and sister chromatid exchanges in cells treated with different chemotherapeutic agents
No full textPurpose: The mismatch repair (MMR) system plays a major role in mediating the cytotoxicity and clastogenicity of agents generating O 6-methylguanine in DNA. Loss of MMR has also been associated with tumor cell resistance to the cytotoxic effects of 6-thio-guanine and cisplatin and with hypersensitivity to N-(2-chloroethyl)-N′ -cyclohexyl-N-nitrosourea (CCNU). The aim of the present investigation was to elucidate the role played by the MMR system in the generation of chromosomal damage in cells exposed to 6-thioguanine, cisplatin or CCNU. Methods: The MMR-proficient cell lines TK6 and HCT116/3-6, and their MMR-deficient counterparts MT1 and HCT116, were treated with 6-thioguanine, cisplatin or CCNU, and analyzed for cell growth inhibition and chromosomal damage. As a control, similar experiments were performed with the methylating agent temozolomide. Results: Cytotoxicity, chromosomal aberrations and sister chromatid exchanges induced by 6-thioguanine and temozolomide were significantly reduced in the MMR-deficient cell lines with respect to their MMR-proficient counterparts. In contrast, although conferring some protection against cytotoxicity, the loss of MMR did not affect cytogenetic damage induced by cisplatin. CCNU produced comparable levels of cytotoxicity, chromosomal aberrations and sister chromatid exchanges in both MMR-proficient and MMR-deficient cell lines. Conclusions: The MMR system is involved in the generation of chromosomal damage in cells exposed to 6-thioguanine. The system does not play a relevant role in the generation of chromosomal damage in cells treated with CDDP and does not confer protection against the clastogenic effects of CCNU, at least in the cell lines investigated
Determination of Intracellular p 19 core protein in HTLV I infected cells by flow microcytometry analysis
No full textInfluence of mismatch repair system and p53 on celi cycle perturbation, apoptosis and chromosomal damage induced by bleomycin
No full textThe antibiotic bleomycin (BLM) is an anticancer drug used for the treatment of a variety of tumors. Similarly to ionizing radiations, its cytotoxic activity is mainly related to the generation of oxygen radicals and, for this reason, BLM is classified as a radiomimetic agent. Here we describe the influence or either the mismatch repair system (MMR) or p53 on cell cycle alterations, apoptosis and chromosomal damage induced by BLM. The MMR-deficient colon carcinoma cell line HCTI16 and its MMR-proficient subline HCTlI6/3-6, both expressing wild-type p53,were transfected with a vector encoding a dominant-negative p53 mutant, or with an empty vector. Four transfected clones having the following phenotypes: MMR-proficient/p53 wild-type, MMR-proficient/p53 mutant, MMR-deficient/p53 wild-type and MMR-deficient/p53 mutant were selected and subjected to BLM treatment. Loss of p53 alone resulted in abrogation of BLM-induced G1 arrest and a higher accumulation of cells in the G2/M phase. Inactivation of p53 was also associated with increased cell sensitivity to apoptosis and chromosomal damage induced by the drug. Loss of MMR function alone was associated with increased cell resistance to G2/M arrest, apoptosis and chromosomal damage caused by bleomycin. Disabling both p53 and MMR function led to abrogation of BLM-induced G1 arrest and to impairment of drug-induced apoptosis, which was however less pronounced than that observed in the MMR deficient/p53 wild-type clone. Chromosomal damage in BLM-treated MMR-deficient clones was lower than in MMR-proficient ones both at 3 and 48 hours after treatment.
In conclusion, our data show that the functional status of both the MMR system and p53 influences cellular responses to bleomycin, being MMR-proficient/p53 mutant cells the most sensitive and MMR-deficient/p53 wild-type cells the most resistant to the drug
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
In vitro inactivation of human O6-alkylguanine DNA alkyltransferase by antitumor triazene compounds
No full textThe cytotoxic and mutagenic properties of antitumor triazene compounds (TZC) have been mainly attributed to their ability to form DNA adducts at the O6 position of guanine. Repair of these lesions is mediated by O6-alkylguanine DNA alkyltransferase (OGAT) in an autoinactivating reaction. Therefore when lesion repair has occurred, cells are depleted of OGAT until synthesis of new enzyme molecules takes place. In this study, we have evaluated the ability of DNA alkylated by different TZC to deplete OGAT activity. Moreover, we have also investigated whether these compounds might inactivate the OGAT enzyme by a direct reaction with the protein. Human OGAT protein was partially purified from insect cells infected with a recombinant baculovirus containing the human OGAT coding sequences. Thereafter human OGAT protein was exposed directly to TZC or to TZC-alkylated DNA. Among the TZC tested, p-(3-methyl-1-triazeno)benzoic acid was the most effective OGAT inactivator by direct interaction with the protein. Moreover DNA substrates treated with methylating TZC, such as temozolomide or p-(3-methyl-1-triazeno)benzoic acid, were more effective in depleting the repair enzyme, compared to DNA pretreated with the chloroethylating TZC mitozolomide. In conclusion, our results show that TZC inactivate in vitro OGAT activity by either direct or indirect mechanisms. Therefore TZC are good candidates for 1) increasing their own cytotoxicity, if used according to appropriate dose and treatment schedules and 2) reversing tumor cell resistance to O6-guanine alkylating agents
A miniaturized cell-mediated cytotoxicity assay with human effector mononuclear cells
No full textA miniaturized method (Microtest, MIT) for detecting natural killer (NK) and antigen-elicited cell-mediated cytotoxicity has been developed. It retains the sensitivity and the efficiency of conventional macroassay (Macrotest, MAT). In comparison with the standard MAT, MIT provides a 5-fold reduction in the number of effector and target cells without changing the final reaction volume. This avoids the excessive relative evaporation that could occur in microassays employing limited reaction volumes. Moreover the use of V-bottom microtiter plates allows the recovery of 0.15 ml of supernatant, thus increasing the efficiency of 51Cr recovery. MIT was adopted for the evaluation of the NK activity of untreated or interferon (IFN)-treated human mononuclear cells (MNC) and for cold-inhibition and cytotoxic T-lymphocyte (CTL) assays. In the experiments performed with both macro and micro assays, comparable values of the percentage of specific lysis and of the number of lytic units were found. The slopes of the curves obtained with MIT are generally slightly lower than those detectable with MAT. The Pearson coefficient r2 is generally better for the macroassay although it can be considered acceptable in the microassay. The MIT described here appears to be a useful method, especially for providing information on natural resistance and cytotoxic T-lymphocyte systems in a number of pathological conditions characterized by a small recovery of effector cells from standard blood collection for analytical purposes
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