Similarities between human ataxia fibroblasts and murine SCID cells: high sensitivity to gamma rays and high frequency of methotrexate-induced DHFR gene amplification, but normal radiosensitivity to densely ionizing alpha particles
| Autor: | Christine Lücke-Huhle |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Cell Survival
Biophysics Mice SCID Biology Radiation Tolerance Ataxia Telangiectasia Mice Immune system Dihydrofolate reductase Gene duplication medicine Animals Humans Radiosensitivity Gene Cells Cultured General Environmental Science Mice Inbred BALB C Radiation Gene Amplification Fibroblasts medicine.disease Alpha Particles Molecular biology Tetrahydrofolate Dehydrogenase Cell killing Methotrexate Cell culture Gamma Rays Ataxia-telangiectasia biology.protein |
| Zdroj: | Radiation and environmental biophysics. 33(3) |
| ISSN: | 0301-634X |
| Popis: | Two gamma-ray hypersensitive cell lines, human ataxia telangiectasia (AT) and murine severe combined immune deficiency (SCID) cells, proved to be very competent in amplifying their dihydrofolate reductase (DHFR) gene under methotrexate selection stress. Over a period of months, methotrexate-resistant clones were obtained which were able to grow in progressively increasing methotrexate concentrations up to 1 mM. By then methotrexate-resistant AT and SCID cells had amplified their DHFR gene 6- and 30-fold, respectively, and showed very high DHFR mRNA expression. In contrast, related cells with normal radiosensitivity (human GM637 and mouse BALB/c fibroblasts) did not show DHFR gene amplification under comparable conditions. This correlation of the capacity of DHFR gene amplification and gamma-ray hypersensitivity in AT and SCID cells suggests that gene amplification may have a mechanism(s) in common with those involved in repair of gamma-radiation-induced damage. No difference in cell killing could be observed following exposure to densely ionizing alpha particles: AT and SCID cells exhibited comparable survival rates to GM637 and BALB/c cells, respectively. |
| Databáze: | OpenAIRE |
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