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DNA repair kinetics in irradiated undifferentiated and terminally differentiated cells

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Summary

The brains of male Fisher 344 rats bearing 80–150 mg intracerebral 9L/Ro tumors were irradiated with doses of 1,250–5,000 rads of x- orγ-rays. At various times after irradiation, the cerebellum and tumor were excised, dissociated into single cells and the DNA from these cells sedimented through alkaline sucrose gradients in zonal rotors with slow gradient reorienting capability. Quantitation of the DNA repair kinetics demonstrated that the process in both tumor cells and neurons has a fast and slow phase. Although all other alternatives cannot be completely eliminated, we suggest that these two phases are most reasonably interpreted as representing repair of lesions in very accessible and less accessible regions of the genome rather than1) repair of different types of lesions such as single-or double-strand breaks or2) removal of immediate breaks and breaks induced during excision repair of latent base damage. The slow repair phase is saturable, but not inducible in both tumor cells and neurons. The data suggest that tumor cells restore their chromosomal DNA structure to the unirradiated state faster than neurons because1) they contain more of the repair system per unit of DNA and2) a larger proportion of their genetic material is comprised of very accessible regions. The data also suggest that the entire tumor cell genome may be accessible to the repair enzyme(s), while it is possible that a portion of the neuronal genome may be completely inaccessible.

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Authors and Affiliations

  1. Department of Radiation Oncology, Rhode Island Hospital, 02902, Providence, RI, USA

    Kenneth T. Wheeler

  2. Cancer Center, University of Rochester, 14642, Rochester, NY, USA

    James V. Wierowski

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  1. Kenneth T. Wheeler
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  2. James V. Wierowski
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Wheeler, K.T., Wierowski, J.V. DNA repair kinetics in irradiated undifferentiated and terminally differentiated cells. Radiat Environ Biophys 22, 3–19 (1983). https://doi.org/10.1007/BF01323757

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