| 1. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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Chromatin- and temperature-dependent modulation of radiation-induced double-strand breaks
- 2003
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 79:10, s. 809-816
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the influence of chromatin organization and scavenging capacity in relation to irradiation temperature on the induction of double-strand breaks (DSB) in structures derived from human diploid fibroblasts. Materials and methods: Agarose plugs with different chromatin structures (intact cells±wortmannin, permeabilized cells with condensed chromatin, nucleoids and DNA) were prepared and irradiated with X-rays at 2 or 37°C and lysed using two different lysis protocols (new ice-cold lysis or standard lysis at 37°C). Induction of DSB was determined by constant-field gel electrophoresis. Results: The dose-modifying factor (DMFtemp) for irradiation at 37 compared with 2°C was 0.92 in intact cells (i.e. more DSB induced at 2°C), but gradually increased to 1.5 in permeabilized cells, 2.2 in nucleoids and 2.6 in naked DNA, suggesting a role of chromatin organization for temperature modulation of DNA damage. In addition, DMFtemp was influenced by the presence of 0.1 M DMSO or 30 mM glutathione, but not by post-irradiation temperature. Conclusion: The protective effect of low temperature was correlated to the indirect effects of ionizing radiation and was not dependent on post-irradiation temperature. Reasons for a dose modifying factor <1 in intact cells are discussed.
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| 2. |
- Kihlmark, Madeleine, et al.
(författare)
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Correlation between nucleocytoplasmic transport and caspase–3-dependent dismantling of nuclear pores during apoptosis
- 2004
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 293:2, s. 346-356
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Tidskriftsartikel (refereegranskat)abstract
- During apoptosis (also called programmed cell death), the chromatin condenses and the DNA is cleaved into oligonucleosomal fragments. Caspases are believed to play a major role in nuclear apoptosis. However, the relation between dismantling of nuclear pores, disruption of the nucleocytoplasmic barrier, and nuclear entry of caspases is unclear. We have analyzed nuclear import of the green fluorescent protein fused to a nuclear localization signal (GFP-NLS) in tissue culture cells undergoing apoptosis. Decreased nuclear accumulation of GFP-NLS could be detected at the onset of nuclear apoptosis manifested as dramatic condensation and redistribution of chromatin toward the nuclear periphery. At this step, dismantling of nuclear pores was already evident as indicated by proteolysis of the nuclear pore membrane protein POM121. Thus, disruption of nuclear compartmentalization correlated with early signs of nuclear pore damage. Both these events clearly preceded massive DNA fragmentation, detected by TUNEL assay. Furthermore, we show that in apoptotic cells, POM121 is specifically cleaved at aspartate-531 in its large C-terminal portion by a caspase-3-dependent mechanism. Cleavage of the C-terminal portion of POM121, which is adjoining the nuclear pore complex, is likely to disrupt interactions with other nuclear pore proteins affecting the stability of the pore complex. A temporal correlation of apoptotic events supports a model where caspase-dependent disassembly of nuclear pores and disruption of the nucleocytoplasmic barrier paves the way for nuclear entry of caspases and subsequent activation of CAD-mediated DNA fragmentation.
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| 3. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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Cleavage of cellular DNA by calicheamicin γ1
- 2003
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Ingår i: DNA Repair. - 1568-7864 .- 1568-7856. ; 2:4, s. 363-374
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Tidskriftsartikel (refereegranskat)abstract
- It is assumed that the efficient antitumor activity of calicheamicin γ1 is mediated by its ability to introduce DNA double-strand breaks in cellular DNA. To test this assumption we have compared calicheamicin γ1-mediated cleavage of cellular DNA and purified plasmid DNA. Cleavage of purified plasmid DNA was not inhibited by excess tRNA or protein indicating that calicheamicin γ1 specifically targets DNA. Cleavage of plasmid DNA was not affected by incubation temperature. In contrast, cleavage of cellular DNA was 45-fold less efficient at 0°C as compared to 37° due to poor cell permeability at low temperatures. The ratio of DNA double-strand breaks (DSB) to single-stranded breaks (SSB) in cellular DNA was 1:3, close to the 1:2 ratio observed when calicheamicin γ1 cleaved purified plasmid DNA. DNA strand breaks introduced by calicheamicin γ1 were evenly distributed in the cell population as measured by the comet assay. Calicheamicin γ1-induced DSBs were repaired slowly but completely and resulted in high levels of H2AX phosphorylation and efficient cell cycle arrest. In addition, the DSB-repair deficient cell line Mo59J was hyper sensitive to calicheamicin γ. The data indicate that DSBs is the crucial damage after calicheamicin γ1 and that calicheamicin γ1-induced DSBs are recognized normally. The high DSB:SSB ratio, specificity for DNA and the even damage distribution makes calicheamicin γ1 a superior drug for studies of the DSB-response and emphasizes its usefulness in treatment of malignant disease.
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| 4. |
- Akre, O, et al.
(författare)
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Body size and testicular cancer
- 2000
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 92:13, s. 1093-1096
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Frängsmyr, L., et al.
(författare)
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Evolution of the carcinoembryonic antigen family. Structures of CGM9, CGM11 and pregnancy-specific glycoprotein promoters
- 2000
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Ingår i: Tumor Biology. - 1010-4283 .- 1423-0380. ; 21:2, s. 63-81
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Tidskriftsartikel (refereegranskat)abstract
- Earlier studies have demonstrated that the genes of the human carcinoembryonic antigen (CEA) family can be divided into three subgroups, the CEA subgroup (n = 12), the pregnancy-specific glycoprotein (PSG) subgroup (n = 11), and a third subgroup (n = 6). To further characterize the CEA gene family, we have determined the genomic structures of CGM9 and CGM11, analyzed the promoter regions of all eleven PSGs, studied the CGM15-PSG13 intergenic region and the evolutionary relationships between the CEA family genes. CGM9, a typical CEA subgroup member, was a pseudogene with the exon structure [5'UTR-L-L/N-TM-Cyt-3'UTR]. CGM11 contained a mixture of exons derived from CEA and PSG subgroup genes. The formula of the CGM11 pseudogene was [5'UTRL- L/N-C-3'UTR]. Thus both genes lacked the IgC2-like domains typically found in CEA subfamily members. The upstream promoter regions of all eleven PSGs were characterized. All PSG promoters lacked the classical TATA and CCAAT elements, but had putative PEA3 box(es), CACCC box(es), a RARE box, and poly (dG-dT) repeats of different lengths. Five PSGs also had an SP1 site. The complete 10-kb intergenic region between CGM15 and PSG13 was sequenced. Clusters of different types of repetitive sequences were seen. The time of divergence of the CEA and PSG subfamilies was estimated to be 107.7 ± 17.1 million years, or at about the time of human-rodent divergence. Models for the evolution of CEA and PSG and the third family subgroup genes are proposed.
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| 6. |
- Lagerlund, M, et al.
(författare)
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Predictors of non-attendance in a population-based mammography screening programme; socio-demographic factors and aspects of health behaviour
- 2000
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Ingår i: European Journal of Cancer Prevention. - : Ovid Technologies (Wolters Kluwer Health). - 0959-8278 .- 1473-5709. ; 9:1, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify predictors of non-attendance in a population-based mammography-screening programme in central Sweden, on the basis of telephone interviews with 434 non-attendees and 515 attendees identified in a mammography register, Non-attendance was studied in relation to sociodemographic factors, indicators of general health behaviour, self-rated health and experience of cancer in others and own cancer or breast problems. Being single or being non-employed were the only important socio-demographic predictors of non-attendance. Non-attendance was more likely among women who never visited a dentist, had not visited a doctor in 5 years, had never used oral contraceptives or hormone replacement therapy, had never had cervical smear tests, never drank alcohol, smoked regularly, reported no breast cancer in family or friends or own breast problems, We conclude that socio-demographic factors alone do not appear to constitute strong predictors of non-attendance, General health behaviour and previous experience of cancer and breast disease seem to be more important factors. Our results suggest that in the setting of population-based outreach mammography programmes, previous contacts with the health care system and encouragement from health professionals represent determinants of attendance.
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