Similarities between human ataxia fibroblasts and murine SCID cells: High sensitivity to γ rays and high frequency of methotrexate-induced DHFR gene amplification, but normal radiosensitivity to densely ionizing α particles

Biophysik - Tập 33 - Trang 201-210 - 1994
Christine Lücke-Huhle1
1Kernforschungszentrum Karlsruhe, Institut für Genetik, Karlsruhe, Germany

Tóm tắt

Twoγ-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 andγ-ray hypersensitivity in AT and SCID cells suggests that gene amplification may have a mechanism(s) in common with those involved in repair ofγ-radiation-induced damage. No difference in cell killing could be observed following exposure to densely ionizing α particles: AT and SCID cells exhibited comparable survival rates to GM637 and BALB/c cells, respectively.

Tài liệu tham khảo

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