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The Radiosensitive Cell Line 180BR Is Not Defective in the Major DNA Damage-sensing Proteins¹

The Queensland Institute of Medical Research, The Bancroft Centre, Herston, Brisbane, Queensland 4029, Australia [H. L., Q. S., M. F. L.]; Medical Research Council, MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton BN1 9RR, United Kingdom [C. A.]; The Department of Surgery, University of Queensland, PO Royal Brisbane Hospital, Herston, Brisbane, Queensland 4029 Australia [M. F. L.]

The fibroblast culture 180BR, established from a patient showing an adverse response to radiotherapy, has been shown previously to be hypersensitive to ionizing radiation and to be defective in the repair of DNA double-strand breaks. We demonstrate here that the products of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and its regulatory subunits (Ku 70 and Ku 80) are present at normal levels and possess functional activity. The product of the gene mutated in the human genetic disorder ataxia-telangiectasia was also detected in these cells. Apoptosis was detected after high-dose ionizing radiation exposure, and this process was accompanied by specific degradation of DNA-PKcs, ATM, and poly(ADP-ribose) polymerase. Activation of CPP32, an interleukin 1ß converting enzyme-like protease implicated in apoptosis, was also observed in 180BR cells in response to radiation damage. The radiosensitivity observed in 180BR cells can be accounted for, at least in part, by radiation-induced apoptosis, and the defect in these cells is not a gross one in DNA-PKcs or ATM.

¹ This work was supported by grants from the Australian National Health and Medical Research Council and the Queensland Cancer Fund. H. L. was supported by a studentship from the Tzu Chi Foundation. H. L. and Q. S. contributed equally to this work.

² To whom requests for reprints should be addressed, at The Queensland Institute of Medical Research, The Bancroft Centre, 300 Herston Road, Herston, Brisbane, Queensland 4029, Australia.

Received 4/ 9/97. Accepted 10/24/97.

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