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Biomedical subjects

M Edgren

Publications and source records attributed to M Edgren.

31 records · Page 2Linked to original sources
PubMed1981

Induction and repair of single-strand DNA breaks after X-irradiation of human fibroblasts deficient in glutathione.

Using the unwinding technique in weak alkali, the induction and repair of DNA single-strand breaks was determined after aerobic and anerobic X-irradiation of human fibroblasts, obtained from a patient suffering from 5-oxoprolinuria, and from a clinically healthy control. The metabolic disorder associated with 5-oxprolinuria is a deficiency in glutathione synthetase activity resulting in a greatly reduced glutathione content in the cells. A small dose-modifying effect of oxygen (o.e.r. = 1.1) was found for these cells in comparison to an o.e.r. of 2.5 for control cells with normal glutathione content. No significant difference was found between the repair capacity of cells with normal and deficient glutathione content, and repair was nearly completed within 60 min of anoxic irradiation in each case. In contrast, after aerobic irradiation of glutathione-deficient cells repaired less than 70 per cent of the breaks during the same period. When the glutathione-deficient cells were incubated with either dithiothreitol or mercaptopropionylglycine directly after aerobic irradiation, almost complete repair was obtained within 60 Min. The data are interpreted as indicating that the repair mechanism for oxically and anoxically induced single-strand breaks is qualitatively different, and requires glutathione in the former case.

Adult↗
PubMed1981

Oxygen enhancement of radiation induced lethality is greatly reduced in glutathione deficient human fibroblasts.

The in vitro clonogenic survival of human fibroblasts with a genetically defined glutathione (GSH) deficiency was studied after irradiation with X-rays in oxygen or in oxygen free argon. Genetically related fibroblasts without GSH deficiency were used as a control. The oxic survival curve of both cell lines was similar. In comparison to the oxic survival curve, the anoxic survival curve of GSH deficient cells indicated an oxygen enhancement ratio (OER) approximately 1.5. An OER approximately 2.9 was calculated in comparing the oxic and anoxic survival curves of the control cell line. The results were discussed in support of the theory according to which oxygen and GSH compete for radiation induced radicals in key molecules, the former irreversibly fixing and the latter repairing the radiation damage.

Anaerobiosis↗
PubMed1980

Lack of oxygen effect in glutathione-deficient human cells in culture.

The frequency of X-ray-induced DNA breaks was determined in human cell lines which are deficient in glutathione synthetase and have a greatly reduced glutathione content. Hydroxyapatite chromatography was used for the estimation of the DNA breaks in cell cultures, which were derived either from lymphoblasts transformed by infection with EB virus or from fibroblasts. The dose-effect relationship for the induction of breaks when radiation exposure was made in argon, was similar to that found when exposure was made in air. In control cultures with normal glutathione content, the induction of breaks was enhanced when irradiation was made under aerobic, instead of anaerobic, conditions. Treatment of the glutathione-deficient cells with the hypoxic radiosensitizer misonidazole did not enhance the induction of breaks by radiation delivered either in air or in argon. In control cultures, radiation induction of breaks was enhanced by misonidazole under anaerobic but not under aerobic conditions. When the glutathione-deficient cells were pretreated with cysteamine however, irradiation in the absence of oxygen resulted in a decreased frequency of DNA breaks.

Cells, Cultured↗
PubMed1977

Effect of radioprotective aminothiols on the induction and repair of single-strand breaks in the DNA of irradiated mammalian cells.

The effect of cysteamine and 2-mercapto-propionyl-glycine on the induction and repair of single-strand breaks in the DNA of Chinese hamster cells by irradiation in vitro in the presence of oxygen or in anoxia was investigated. The substances protected against the formation of breaks by irradiation both under oxic and anoxic conditions. The substances also exhibited a toxic effect which resulted in degradation of DNA. Cysteamine inhibited the rejoining of breaks after radiation exposure.

Amino Acids, Sulfur↗
PubMedDate not supplied

Serum concentrations of VEGF and b-FGF in renal cell, prostate and urinary bladder carcinomas.

Sixty nine patients with urogenital cancers (renal, bladder and prostate cancer) were studied to determine whether the serum concentrations of Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (b-FGF) reflected the status of the patients and/or the prognosis of the disease. Of the patients included in this study, renal cell carcinoma patients expressed the highest levels of VEGF indicating that these tumours are more VEGF dependent. The values of b-FGF could be considered normal in all three malignancies. No correlation was observed between the expression of VEGF and b-FGF, nor between VEGF and b-FGF and patients survival.

Adult↗
PubMedDate not supplied

Melphalan-induced DNA cross-linking in human melanoma cells and phytohaemagglutinin-stimulated lymphocytes in relation to intracellular drug content and cellular levels of glutathione.

Melphalan-induced DNA cross-linking was compared in a human melanoma cell line (RPMI 8322) and in phytohaemagglutinin (PHA)-stimulated lymphocytes. In both cell types a delayed induction of DNA cross-links was observed, with maximum DNA cross-linking occurring 6-12 hours after drug exposure. Significantly higher peak levels of DNA cross-links were found in PHA-stimulated lymphocytes, total DNA cross-linking being 2.5 times and DNA interstrand cross-linking 2.2 times higher. The intracellular content of free melphalan was 1.3-fold higher in RPMI 8322 cells, thus the lower DNA cross-linking was not due to a lower drug concentration in these cells. RPMI 8322 cells had a 1.8-fold higher level of glutathione, possibly indicating a higher capacity of these cells to inactivate melphalan.

Cell Line↗
PubMedDate not supplied

Neuroendocrine markers; chromogranin, pancreastatin and serotonin in the management of patients with advanced renal cell carcinoma.

A fraction of patients with renal cell carcinoma (RCC) exhibit elevated plasma levels of neuroendocrine (NE) markers, including chromogranin (Cg) A and B, pancreastatin and serotonin. This may suggest neuroendocrine involvement in human RCC. Twenty eight patients (24 men and 4 women) with advanced RCC were included in this study. The ongoing therapy was either tamoxifen, or interleukin-2 (IL-2); alpha interferon and tamoxifen. Plasma analyses of NE markers revealed elevated levels of CgA and serotonin in 28/28 (100%) patients. CgB was elevated in 5/16 (31%) patients, whereas no elevation of pancreastatin was observed in these 16/28 patients. Although the plasma levels of NE markers did not statistically or significantly influence the prognosis of the disease it was observed that patients with elevated NE markers had a less aggressive disease and lived longer than patients with normal or only slightly elevated NE markers. Immunohistochemical analyses of tumour specimens from 10 patients were chromogranin, serotonin and synaptophysin negative, but all were neurone-specific enolase (NSE) positive. The results obtained are of interest. However, extended studies are needed to define the role of these NE markers in the clinical management of patients with RCC.

Adult↗
PubMedDate not supplied

Biological characteristics of adrenocortical carcinoma: a study of p53, IGF, EGF-r, Ki-67 and PCNA in 17 adrenocortical carcinomas.

Adrenocortical carcinoma (ACC) is a rare neoplasm with a poor prognosis. Prognostic factors are needed to identify patients who should be treated aggressively and those for which a less aggressive approach is warranted. As a result of advances within the field of immunohistochemistry, investigations of Ki-67, PCNA, IGF, EGF-r and p53 were performed in 17 ACC. The aim of this study was to clarify the role of Ki-67, PCNA, EGF-r, IGF and p53 in correlation to tumour behaviour and outcome. This retrospective study includes 16 patients, 10 women and 6 men, with a median age of 46 years. Nine tumours were hormonally functioning and 7 were non-functioning. The results obtained revealed that all tumours expressed PCNA and Ki-67 with median values of 59% and 14%, respectively, while p53 was negative in 88%, IGF negative in 82% and EGF-r positive in 94% of the tumours. No correlation was found between p53, IGF, EGF-r and survival rate. There was no interdependence between PCNA and Ki-67, or between PCNA, Ki-67 and the survival rate.

Adrenal Cortex Neoplasms↗