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Dose Response Curve (dose + response_curve)
Selected AbstractsCentrosome amplification induced by the antiretroviral nucleoside reverse transcriptase inhibitors lamivudine, stavudine, and didanosineENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2009Mia Yu Abstract In cultured cells, exposure to the nucleoside reverse transcriptase inhibitor (NRTI) zidovudine (AZT) induces genomic instability, cell cycle arrest, micronuclei, sister chromatid exchanges, and shortened telomeres. In previous studies, we demonstrated AZT-induced centrosome amplification (>2 centrosomes/cell). Here, we investigate centrosome amplification in cells exposed to other commonly used NRTIs. Experiments were performed using Chinese Hamster ovary (CHO) cells, and two normal human mammary epithelial cell (NHMEC) strains: M99005 and M98040, which are high and low incorporators of AZT into DNA, respectively. Cells were exposed for 24 hr to lamivudine (3TC), stavudine (d4T), didanosine (ddI), and thymidine, and stained with anti-pericentrin antibody. Dose response curves were performed to determine cytotoxicity and a lower concentration at near plasma levels and a 10 fold higher concentration were chosen for the experiments. In CHO cells, there was a concentration-dependent, significant (P < 0.05) increase in centrosome amplification for each of the NRTIs. In NHMEC strain M99005, an NRTI-induced increase (P < 0.05) in centrosome amplification was observed for the high concentrations of each NRTI and the low doses of 3TC and ddI. In NHMEC strain M98040, the high doses of ddI and d4T showed significant increases in centrosome amplification. Functional viability of amplified centrosomes was assessed by arresting microtubule nucleation with nocodazole. In cells with more than two centrosomes, the ability to recover microtubule nucleation was similar to that of unexposed cells. We conclude that centrosome amplification is a consequence of exposure to NRTIs and that cells with centrosome amplification are able to accomplish cell division. Environ. Mol. Mutagen., 2009. © 2009 Wiley-Liss, Inc. [source] The cause and prevention of human birth defects: What have we learned in the past 50 years?CONGENITAL ANOMALIES, Issue 1 2001Robert L. Brent ABSTRACT This review article dealig with the subject of "The Cause and Prevention of Human Birth Defects" was prepared in celebration of the 40th anniversary of the Japanese Teratology Society. It begins with recollections of some of the important contributions of Japanese scientists in the fields of teratology and embryology and a summary of the many scientific and medical accomplishments of the past 50 years in the fields of teratology, genetics, developmental biology, epidemiology and genetics. The review includes a summary of the drugs, chemicals and physical agents that have been documented to result in congenital malformations and reproductive effects when pregnant women are exposed during pregnancy. The principles of teratology were also summarized and emphasize that 1) no teratogenic agent can be described qualitatively as a teratogen, since a teratogenic exposure must include not only the agent, but also the dose and the time in pregnancy when the exposure occurs. 2) Even agents that have been demonstrated to result in malformatins cannot produce every type of malformation. 3) Known teratogens can be presumptively identified by the spectrum of malformations they produce. 4) It is easier to exclude an agent as a cause of birth defects than to definitively conclude that it was responsible for birth defects. 5) When evaluating the risk of exposures, the dose is a crucial component in determining the risk. 6) Teratogenic agents follow a toxicological dose response curve. This means that each teratogen has a threshold dose, below which, there is no risk of teratogenensis, no matter when in pregnancy the exposure occurred. 7) The evaluation of a child with congenital malformations connot be adequately performed unless it is approached with the same scholarship and detail, as is any other complicated medical problem. 8) Each physician must recognize the consequences of providing erroneous reproductive risks to pregnant women exposed to drugs and chemicals during pregnancy or alleging that a child's malformations are due to an environmental agent without performing a complete and scholarly evaluation. [source] Increased Glycosaminoglycans Production in Sclerosing Basal Cell Carcinoma-Derived Fibroblasts and Stimulation of Normal Skin Fibroblast Glycosaminoglycans Production by a Cytokine-Derived from Sclerosing Basal Cell CarcinomaDERMATOLOGIC SURGERY, Issue 11 2000Ronald L. Moy MD Sclerosing basal cell carcinoma (S-BCC) is characterized by an abundant stroma. There is evidence that some tumor cells secrete cytokines that are mitogenic for stromal fibroblasts (FBs). From this study we report increased glycosaminoglycan (GAG) production by cultures of S-BCC FBs in comparison to cultures of nodular BCC (N-BCC) FBs and normal skin FBs. GAG production was measured by cetylpyridinium chloride precipitation of incorporated [3H]-glucosamine. The sclerosing BCC FBs demonstrated a significant increase in production of GAG over control FBs (P < .001) and over N-BCC FBs (P < .001). Values reported as a mean percentage ± SEM for GAG production by S-BCC over control normal skin FBs are 359 ± 28 and over N-BCC FBs are 266 ± 27. In additional experiments, cell extract dilutions from S-BCC tumor, normal dermis, and normal epidermis were incubated with cultures of normal skin FBs. S-BCC-conditioned media was also incubated with normal FBs and GAG production was measured. For both S-BCC extracts and conditioned media, a dose response curve was established showing increased GAG production by normal FBs in relation to increasing the concentration of S-BCC extract or conditioned media. When S-BCC extract was added to normal FBs there was increased GAG production in comparison to normal FBs incubated with dermal or epidermal extracts (P < .001) for both. Two growth factors, transforming growth factor-, (TGF-,) and platelet-derived growth factor (PDGF), already known to be mitogenic for FBs, were incubated with N-BCC and normal FBs in an effort to elucidate the potential cytokine(s) released by S-BCC, causing increased GAG production by surrounding FBs. Neither of these cytokines proved to be effective in promoting a significant increase in GAG production. Our findings support the hypothesis that BCCs release factors that alter stromal FB production of GAG. [source] Flow cytometry peripheral blood micronucleus test in vivo: Determination of potential thresholds for aneuploidy induced by spindle poisonsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2010Zoryana Cammerer Abstract Non-DNA binding genotoxins (e.g., aneugens), unlike DNA-binding genotoxins, are theoretically expected to show thresholded concentration-effect response curves. This is a major issue in genetic toxicology testing because the identification of thresholds in vivo can provide a safety margin for exposure to a particular compound. In the current study we measured micronucleus induction by flow cytometry to determine the dose-response curves for tubulin interacting agents, a specific class of aneugens. All experiments with aneugens, which include colchicine, vinblastine, vincristine, as well as the clastogen cyclophosphamide (CP) were performed in mice to avoid the splenic elimination of micronucleated reticulocytes, which has been described in rats. Flow cytometry analysis revealed a non-linear dose-dependent increase in micronuclei frequencies for all tested aneugens, and a linear dose response curve for the clastogen, CP. To determine whether micronucleus induction at higher doses was due to chromosome loss (aneuploidy) or chromosome breakage (clastogenicity), flow sorting of the micronucleated reticulocytes and fluorescent in situ hybridization (FISH) with a mouse pan centromeric probe were performed for vinblastine, vincristine, and colchicine. Statistical evaluation of the flow cytometry and FISH data was performed to determine the threshold levels for chromosome loss in vivo. The threshold concentrations for vinblastine, vincristine, and colchicine were found at 0.35, 0.017, and 0.49 mg kg,1, respectively. Environ. Mol. Mutagen., 2010. © 2009 Wiley-Liss, Inc. [source] Comparative study of TL created in undoped CVD diamond by , rays, UV and visible lightPHYSICA STATUS SOLIDI (A) APPLICATIONS AND MATERIALS SCIENCE, Issue 9 2010V. Chernov Abstract The thermoluminescence (TL) properties of CVD diamond film irradiated with , rays and illuminated with UV and visible light (200,450,nm) have been studied. The film (23,µm) was grown for 47,h on monocrystalline silicon. The TL glow curves are similar for , irradiation and short wavelength UV light. The , dose response curves and UV light time response curves exhibit linear,supralinear,sublinear behaviour. The structure of the glow curve was determined by a simultaneous deconvolution of a set of curves recorded after preliminary heating to various temperatures. One set of the TL peak parameters was found for all the curves during the deconvolution. The TL glow curves were found to consist of five strongly overlapped peaks. The peaks at about 350 and 400,K obey first-order kinetics. The next three peaks at about 480, 540 and 580,K are described well by general-order kinetics. The TL curves created with light of wavelength between 250 and 450,nm are different from those created by , radiation and short wavelength UV light. The former have low sensitivity and consist of several strongly overlapped peaks, two of them are observed at about 330 and 600,K. [source] | ||||||||||