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Biomedical subjects

M Holmberg

Publications and source records attributed to M Holmberg.

At least 73 records · Page 4Linked to original sources
PubMed1989

The effect of deoxynucleosides on repair of DNA breaks in UVC-irradiated human lymphocytes.

UVC irradiation of mammalian cells induces DNA lesions, which can give rise to transient DNA breaks at subsequent incubation of the cells. The yield of these transient DNA breaks depends on the incision rate as well as on the polymerase and ligation rates. It has previously been shown that the yield of transient DNA breaks is drastically lowered in human lymphocytes if the 4 deoxynucleosides are added to the culture medium during the repair period after UVC irradiation. The present results show that addition of the combination dAdo dGuo dThd or addition of the combination dAdo dThd also efficiently reduces the yield of transient DNA breaks during a repair period of 3 h after the UVC irradiation. Other combinations of deoxynucleosides are less efficient or not efficient at all. This indicates that the pool sizes of dATP and dTTP affect the yield of transient DNA breaks in human lymphocytes. However, the present data also indicate that the number of processed repair sites does not increase during the repair period after UVC irradiation, if the combination dAdo dThd is present in the culture medium during the repair period. Therefore, it is proposed that the presence of dAdo dThd affects the rate of insertion of repair patches but not the total amount of synthesized and inserted patches.

Cells, Cultured↗
PubMed1988

Simultaneous detection of DNA strand breaks and unscheduled DNA synthesis in mutagen-treated human lymphocytes in the absence of hydroxyurea.

Human lymphocytes in the quiescent state were exposed to UVC radiation. After irradiation the cells were allowed to repair for various times in the presence of [3H]thymidine or [3H]deoxycytidine in the culture medium. Hydroxyurea was not used to suppress semiconservative DNA replication in the small number of growing cells. After incubation DNA strand breaks were detected by the DNA-unwinding method and the amount of 3H incorporation in DNA was measured by liquid scintillation counting. The results show that the yield of DNA strand breaks and the amount of unscheduled DNA synthesis (UDS) can be measured from the same lymphocyte sample. A low background 3H incorporation in untreated cells could be achieved even in the absence of hydroxyurea. This requires, however, that 3H incorporation is measured only in the double-stranded DNA and that [3H]dCyd is used instead of [3H]dThd as the labelled deoxynucleoside.

Chromatography↗
PubMed1988

Radiation doses in Sweden resulting from the Chernobyl fallout: a review.

The risk associated with the Chernobyl fallout is the product of radiation dose and risk factor per dose unit. The radiation doses originate from inhalation of radioactive particles, ground irradiation from deposited nuclides and internal irradiation caused by contaminated food. In Sweden the largest dose contribution is due to external radiation. The deposition has been mapped by aerial measurements and in situ high-resolution gamma measurements at ground level over the whole country. On the basis of these measurements, population-weighted doses for external radiation have been estimated. Whole-body measurements on randomly selected individuals have been performed in order to estimate the average dose from internal irradiation. The collective dose, i.e. the sum of all individual doses, has been estimated to be about 1500 man-Sievert for the first year after Chernobyl and 5000-7000 man-Sievert for a 50-year period. Using a risk factor of 0.02 fatal cancers per man-Sievert the Chernobyl fallout over Sweden might cause 100-200 fatal cancers.

Accidents↗
PubMed1987

Use of a DNA hybridization assay for the detection of Plasmodium falciparum in field trials.

A DNA probe consisting of 21 base pair repeats obtained from a Tanzanian isolate of Plasmodium falciparum, cloned in pBR322 and labeled with 32P by nick translation was used to detect malaria parasitemia in samples obtained during a malaria survey undertaken in The Gambia. In an initial trial the hybridization assay had a specificity for P. falciparum of 100% and a sensitivity of 68%. False negative results were obtained only on samples with low parasitemia. Assay of red cells collected during an earlier malaria survey which had been stored for 1 year at -20 degrees C gave a higher level of sensitivity (85%), suggesting a beneficial effect from freezing and thawing. This was confirmed by examining in the same assay red cells processed immediately after collection and after 2 weeks of storage at -20 degrees C. Freezing and thawing gave a 21% increase in positivity, and a sensitivity of 100% was achieved with the frozen samples. Quantitation of autoradiographs by visual inspection and by scintillation counting gave a reasonable correlation with parasite counts. The DNA hybridization assay has considerable promise as an epidemiological tool.

Animals↗
PubMed1986

The role of short-lived DNA lesions in the production of chromosome-exchange aberrations.

Human lymphocytes were treated with combined UVC radiation and X-rays or they were X-irradiated and incubated for 60-90 min in the presence of the DNA-repair inhibitor ara-C. The X-ray-induced chromosome exchange aberration yield was enhanced both by UVC and ara-C. approximately a factor of two in the linear (low dose) portion of the dose-response curve. The enhancement was small in the dose squared (high dose) portion where previous dose-fractionation experiments have shown that X-ray-induced lesions leading to aberrations exist for several hours. The yield of aberrations in lymphocytes incubated after irradiation in the presence of ara-C reaches a saturation level almost immediately after irradiation (5-15 min). These cytogenetic observations together with a previous finding (Holmberg and Strausmanis, 1983) give direct and indirect evidence that the enhanced aberration yield is due to short-lived DNA breaks formed immediately after X-irradiation. Measurements on the repair kinetics of the DNA breaks induced by X-irradiation show that ara-C strongly impairs the repair of short-lived X-ray-induced DNA breaks. It was also observed that the DNA breaks generated after UVC irradiation occur almost immediately after irradiation and the level of these transient DNA breaks reaches saturation even for short incubation times. Thus, the repair of these breaks can complete with the repair of short-lived X-ray-induced DNA-breaks in combined irradiation with UVC and X-rays. The experimental results can be explained on the assumption that X-ray-induced aberrations originate from exchange complexes formed in interactions between both short-lived and long-lived DNA breaks. The short-lived DNA breaks give rise to exchange complexes mainly within single ionization tracks where the DNA breaks are close together. The time between irradiation and exchange complex formation is of the order of 5-15 min within such a track, and short-lived breaks might be repaired before complexes have been formed. If the DNA repair of these breaks is delayed by UVC or ara-C treatment this results in a higher probability of exchange-complex formation. In contrast, interactions between breaks in different tracks originate from long-lived DNA breaks and the probability for complex formation from these breaks is not markedly affected by UVC or ara-C.

Cells, Cultured↗
PubMed1986

Diagnosis of Plasmodium falciparum infection by spot hybridization assay: specificity, sensitivity, and field applicability.

The spot hybridization assay for the detection of Plasmodium falciparum reported here uses as probe a repetitive DNA sequence from this species and exhibits a high degree of species specificity. Isolates from African, Asian, and South American patients were positive in the assay and gametocytes could be detected at the same level of parasitaemia as asexual parasites. An RNA probe containing the same repetitive sequence as the DNA probe has a detection limit of 1 parasite per 10(6) red blood cells. Comparison of the results of the assay with those obtained by microscopic examination of blood films indicated that the assay was more sensitive than microscopy if the blood films were examined for only 10 minutes; however, 40 minutes' examination by microscopy was slightly more sensitive than the assay.

DNA↗
PubMed1985

Simultaneous detection of SCE and Q-bands on human chromosomes by a double-staining technique.

Human lymphocytes were cultured for two cell cycles in the presence of bromodeoxyuridine (BrdU), and the resulting metaphase chromosomes were first stained with quinacrine mustard (QM) and then, immediately afterwards, with Hoechst 33258, without any intermediate destaining. Both Q-banding patterns and sister chromatid differential staining were photographed subsequently on the same metaphase using two different filter blocks of the fluorescence microscope.

Bisbenzimidazole↗
PubMed1983

The repair of chromosome aberrations in human lymphocytes after combined irradiation with UV-radiation (254 nm) and X-rays.

Human lymphocytes were exposed to UV-radiation and X-rays. The previously reported synergistic effect on the frequency of chromosome aberrations (Holmberg and Jonasson, 1974) was measured as a function of the time between the 2 irradiations to study the effect of repair processes in cells in PBS at 20 degrees C. The synergistic effect was found to be rather constant as a function of time (in the interval up to 90 min) when the UV-radiation is delivered first. The synergistic effect decreases with a half-life of about 20 min when the cells are first X-irradiated and after various times are given a UV-treatment. This is not in accordance with findings from dose-fractionation experiments with X-rays, in which lesions interact with each other for several hours. It is proposed that the enhanced aberration frequency in the combined irradiations originates from interactions between short-lived, X-ray-induced DNA-lesions in close spatial proximity (mainly lesions in the same ionization track), and the repair of these lesions are affected by the UV-treatment. In contrast, the aberrations studied in dose-fractionation experiments, by definition, are due to interactions between (long-lived) lesions in different tracks. Further details of this model for aberration production are discussed.

Cells, Cultured↗
PubMed1979

Prevalence of tenosynovitis and other injuries of the upper extremities in repetitive work.

The purpose of this investigation was to compare the prevalence of soft tissue disorders in the neck, arms and hands between packers doing repetitive work and shop assistants with variable tasks. One hundred and fifty-two female assembly-line packers in a food production factory and 133 female shop assistants were interviewed about their symptoms and given a clinical examination of the neck and upper extremities. The number of cases of tension neck, cervical syndrome, scalenus syndrome, and humeral epicondylitis did not differ significantly between the two groups. The prevalence of tenosynovitis and humeral tendinitis was significantly higher for the assembly-line packers. The packing work consisted of static muscle work by the arms, grasping and maximal extensions of the fingers, and lateral deviations of the wrists. The movements numbered up to 25,000/workday. A relationship between some work load factors and some disorders of the upper extremities is probable.

Acromioclavicular Joint↗
PubMed1978

Lack of effect on the chromosomal non-disjunction in aged female mice after low dose X-irradiation.

Karyotypes were determined in 1064 embryos of aged C57/BL mothers. The virgin female mice were irradiated with 0, 4, 8 or 16 R of X-rays, respectively, and placed with young untreated males 5 days after irradiation. 10.5-days old embryos were recovered from the uterus. Aneuploid embryos classified as alive (heart beats observed at the dissection) were 1 monosomic in the control group (496 embryos) and 2 trisomics in the irradiated group (568 embryos). The number of aneuploid embryos classified as dead was 4 trisomic cases in the control group and 3 trisomics in the irradiated group. The data indicate that trisomic embryos are not uncommon in the mouse but are eliminated in post-implantation death. In contrast to the results of Yamamoto et al. the present data do not demonstrate an increased frequency of chromosome abnormalities in embryos of aged mice X-irradiated before mating as compared to non-irradiated ones.

Aging↗
PubMed1976

Lack of synergistic effect between X-ray and UV irradiation on the frequency of chromosome aberrations in PHA-stimulated human lymphocytes in the G1 stage.

PHA-stimulated human lymphocytes in the G1 stage were irradiated with UV radiation and X-rays, and the cells were analyzed for chromosomal aberrations in the first mitotic division. The frequency of dicentric chromosomes after single X-irradiation in the G1 stage was about twice the yield in the G0 stage. No increase in the yield of dicentrics was observed after combined irradiation with UV and X-rays. This is contrary to the finding for G0 lymphocytes, where a 2-fold increase of chromosome aberrations was observed. UV irradiation of G1 lymphocytes induced chromatid-type aberrations whereas no significant yield of dicentric chromosomes was observed. This is in agreement with previous findings in Chinese hamster cells in the G1 stage [7]. Irradiation of G0 lymphocytes with UV radiation induce a low frequency of dicentric chromosomes. Thus, the present data indicate that the ratio between chromosome-type and chromatid-type aberrations is different in the G1 and G0 stages in human lymphocytes irradiated with UV radiation.

Chromosome Aberrations↗
PubMed1975

Genetic effects of acute and chronic irradiation with 14 MeV neutrons.

Male CBA mice were exposed to 14.5 MeV neutron, either in an acute (150 or 250 rad) or a chronic dose (250 rad) and the genetic effects of the irradiations were compared. No detectable difference in the rate of mutations existed between acute and chronic exposure, with these neutrons.

Animals↗