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Biomedical subjects

U Ringborg

Publications and source records attributed to U Ringborg.

At least 127 records · Page 7Linked to original sources

Different activities of unscheduled DNA synthesis in human melanoma and bone marrow cells.

Unscheduled DNA synthesis (UDS) indicated by melphalan was studied in freshly collected tumor cells from human melanoma metastases. Comparative studies were done on human bone marrow blast cells. Significant levels of UDS comparable with those in myeloblasts were found in only two of eight melanoma cell populations. This difference between melanoma and blast cells was not related to different cellular uptake of melphalan. When UDS was induced by ultraviolet irradiation, significant levels of UDS were found in all melanoma and blast cell populations studied. Also, in a human melanoma cell line, high levels of UDS were found after exposure to ultraviolet irradiation, while treatment with melphalan did not result in detectable levels of UDS. Possible explanations for the divergent results of UDS in melphalan-exposed melanoma cells are discussed.

Bone Marrow↗

Flow cytofluorometric DNA analyses of metastases of human malignant melanomas.

Flow cytofluorometric analyses of DNA content were performed on 38 subcutaneous and lymph node metastases from 32 patients with malignant melanoma. Cells from 8 tumors had DNA patterns corresponding to diploid DNA values, and the remaining 30 had aneuploid cell populations, mostly in the diploid to tetraploid region. Eight tumors contained more than one cell population. The number of S-phase cells varied from 3% to 34%. The number of S-phase cells was significantly higher in aneuploid as compared to diploid cell populations. Patients with a proportion of S-phase cells greater than or equal to 10% had a significantly shorter survival time as compared to patients with less than 10% S-phase cells.

DNA, Neoplasm↗

Decreased UV-induced DNA repair synthesis in peripheral leukocytes from patients with the nevoid basal cell carcinoma syndrome.

The UV-induced DNA repair synthesis in peripheral leukocytes from 7 patients with the nevoid basal cell carcinoma syndrome was compared to that in peripheral leukocytes from 5 patients with basal cell carcinomas and 39 healthy subjects. A dose response curve was established for each individual, and maximum DNA repair synthesis was used as a measure of the capacity for DNA repair. The patients with the nevoid basal cell carcinoma syndrome had about 25% lower level of maximum DNA repair synthesis as compared to the patients with basal cell carcinomas and control individuals. The possibility that DNA repair mechanisms may be involved in the etiology to the nevoid basal cell carcinoma syndrome is discussed.

Adult↗

Human monocytes and lymphocytes differ in the rate of DNA repair synthesis and viability after exposure to nitrogen mustard.

Unscheduled DNA synthesis was studied in human lymphocytes and monocytes after treatment with nitrogen mustard, methyl-methane-sulphonate and ultraviolet irradiation. The unscheduled DNA synthesis was about 4 times higher in monocytes than in lymphocytes after treatment with nitrogen mustard. Treatment with methyl-methane-sulphonate or ultraviolet irradiation confirmed the higher capacity for unscheduled DNA synthesis in the monocytes. When Ficoll-Isopaque-isolated mononuclear cells were exposed to various doses of nitrogen mustard and incubated for different periods, a dose- and time-dependent increase in trypan blue uptake was found. Furthermore, a corresponding dose- and time-dependent decrease was noted in 3H-uridine incorporation. Since trypan blue uptake will not enable differentiation between monocytes and lymphocytes appearing as a mixed cell population, 3H-uridine flash labeling index was studied after exposure to nitrogen mustard. There was a dose- and time-dependent decrease in 3H-uridine labeling index, suggesting a correlation between the absence of 3H-uridine incorporation and increase in trypan blue uptake. When compared to monocytes, the lymphocytes were more affected in this respect after exposure to nitrogen mustard. The possibility that differences in cytotoxic effect may be related to DNA repair mechanisms is discussed.

DNA↗

Further evidence for increased light sensitivity in patients with malignant melanoma.

Minimal erythema dose (MED), immediate pigment darkening (IPD) and skin typing were performed on 130 patients with malignant melanoma and on seventy-three controls. The tumours were histologically classified according to Clark as superficial spreading melanoma, nodular melanoma, and lentigo maligna melanoma. The tumours of twelve patients were not possible to classify. Patients belonging to skin type IV and patients with lentigo maligna melanoma had a significantly higher mean age. The IPD reaction was significantly higher in skin type II than in skin types III and IV both in patients and in controls. IPD and MED showed no significant correlation to age and sex. MED was significantly lower among patients with malignant melanoma than controls. These data indicate that light sensitivity is of aetiological importance in malignant melanoma.

Age Factors↗

Treatment of carcinoma of the head and neck with combined irradiation and chemotherapy.

Radiation therapy was combined with simultaneous administration of bleomycin, cyclophosphamide and 5-fluorouracil for the treatment of 33 patients with carcinoma of the head and neck. This combination increased the toxicity to the normal tissue. Complete response was obtained in 46 per cent, partial response in 36 per cent and no response in 18 per cent. Patients with a complete response had a significantly longer survival than patients with a partial or no response. An increased cytotoxicity was noted after the combined treatment when compared with irradiation alone. However, no evidence of an increased therapeutic effect was obtained with the addition of simultaneous chemotherapy to irradiation.

Bleomycin↗

Normal UV-induced DNA repair synthesis in peripheral leukocytes from patients with malignant melanoma of the skin.

Seventeen patients with malignant melanoma were compared to 24 control subjects regarding UV-induced DNA repair synthesis. Peripheral leukocytes were irradiated with different UV-doses and the DNA-repair synthesis was measured in presence of hydroxyurea. A dose response curve was established for each individual. No statistical differences were observed when melanoma patients were compared to the controls.

Aged↗

Induction of unscheduled DNA synthesis in human myeloma cells.

Unscheduled DNA synthesis (UDS) induced by melphalan, nitrogen mustard and ultra-violet irradiation was studied in bone marrow cells from myeloma patients. In a previous study, normal bone marrow cells in various stages of maturation were found to display a gradual decrease in UDS parallel with the process of maturation. Myeloma cells showed a similar pattern. Poorly differentiated myeloma cells exhibited a similar level of UDS to myeloblasts and erythroblasts. Irrespective of which repair-inducing agent was used, the relationship between the levels of UDS in the various cell types was constant. This indicates that the differences in the level of UDS in the various cell types was not due to differences in the uptake of the repair-inducing agent.

Alkylating Agents↗

Absence of genotoxic effects of metronidazole and two of its urinary metabolites on human lymphocytes in vitro.

The antiprotozoan agent metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) and two of its major human urinary excretion products, 2-methyl-5-nitromidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole were tested for genotoxic activity in human lymphocytes in vitro by analysis of chromosome aberrations, sister-chromatid exchanges and DNA-repair synthesis. The positive control compounds methyl methanesulphonate (MMS) and nitrogen mustard (HN2) showed significant genotoxic activity in these tests. No such activity of metronidazole and its two metabolites was detected in concentrations up to 1000 microgram/ml (5.8 X 10(-3) M). Nor did these 3 compounds influence DNA-repair synthesis induced by MMS and HN2. These results suggest that metronidazole, 2-methyl-5-nitroimidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole have no direct genotoxic effect on human lymphocytes in vitro.

Chromatids↗

Age-related decrease of ultraviolet light-induced DNA repair synthesis in human peripheral leukocytes.

The capacity for ultraviolet light-induced DNA repair synthesis, studied in peripheral leukocytes from 58 healthy subjects 13 to 94 years old, was found to vary greatly between individuals. A negative, statistically significant correlation was obtained between age and this synthesis, indicating a decrease in repair capacity with age. An age-related decrease in DNA repair may increase the susceptibility of cells to agents causing DNA damage, i.e. carcinogens and certain cytostatic drugs.

Adolescent↗

Induction of unscheduled DNA synthesis in human bone marrow cells by bifunctional alkylating agents.

A technique has been developed for handling human bone marrow cells intended for the examination of DNA repair synthesis. DNA-repair synthesis, induced by melphalan and nitrogen mustard, was measured as the incorporation of 3H-thymidine, registered by autoradiography as unscheduled DNA synthesis (UDS). Comparison of various cell populations disclosed considerable differences in their UDS level, this generally being greatest for the blast populations. During maturation of both myelopoietic and erythropoietic cells, there was a decrease in the UDS level, which was lowest for the end-cell stage. The lymphocytes and monocytes differed considerably in their capacity for UDS. The developed technique would appear to offer an opportunity for determining the capacity for DNA-repair synthesis in malignant bone marrow cells, a factor that has been linked to sensitivity to alkylating agents.

Alkylating Agents↗

Factors responsible for bone marrow toxicity after treatment of myeloma patients with different alkylating agents.

Leukopenia and thrombocytopenia were studied after loading doses of melphalan (5 mg/daily for 18-25 days) in 71 myeloma patients. Seventy per cent of the patients developed pronounced leukopenia (white cells less than 2.0 X 10(9)/l) and/or thrombocytopenia (platelets less than 100 X 10(9)/l). The patients with pronounced and moderate hematological side-effects, respectively, were compared for weight and age. The body weight was the same in the two groups, indicating that the patient's weight is of minor importance for the dosage of melphalan. There was a numerical difference in age, on the borderline for statistical significance, indicating that the age of the myeloma patient may be of minor importance for the dosage of melphalan. It is possible that more pronounced age differences may be of greater importance in this respect. Fifteen patients with myeloma were treated with cyclophosphamide. Compared with melphalan, the effect on white cells was the smae, while the incidence of thrombocytopenia was statistically significantly lower with cyclophosphamide.

Aged↗

Sister chromatid exchanges in lymphocyte cultures of patients receiving chemotherapy for malignant disorders.

The frequency of sister chromatid exchange (SCE) was studied in peripheral lymphocytes of patients receiving chemotherapy for various malignant disorders. Significantly increased SCE frequencies were recorded in six patients 2-7 weeks after CCNU treatment and in one patient 2 weeks after melphalan treatment. One patient treated with prednimustine and one treated with DTIC had SCE frequencies just within the upper limit of the control range 1-2 weeks after therapy. Normal SCE frequencies were recorded in nine patients studied at times varying from 3 days to several weeks after administration of cytostatic courses involving 5-fluorouracil, vincristine, adriamycin, cyclophosphamide, bleomycin, thioTEPA, methotrexate, and prednimustine. Radiotherapy could not be causally related to increased SCE frequencies in any of the patients. The results indicate that CCNU and melphalan, in contrast to several other chemotherapeutic agents, induce very long-lived DNA lesions, which may be of crucial importance for the development of secondary neoplasms.

Adolescent↗