Alterations in p53 do not correlate with radioresistant DNA synthesis.
The radiation hypersensitivity disorder ataxia-telangiectasia (A-T) is uniquely characterized by a failure to immediately inhibit DNA synthesis in response to low dose ionizing radiation which is referred to as radioresistant DNA synthesis (RDS). As it remains controversial as to whether p53 abnormalities are central to RDS and the A-T radiation hypersensitivity disorder, post-irradiation p53 responses and cell cycle alterations were investigated in EBV immortalized B cells (LCL's) from normal individuals (N LCL's) and A-T patients (A-T LCL's). Here it is shown that mutations in p53 are insufficient to give cells such as HL-60 cells RDS potential. Furthermore, RDS which is demonstrable at 2 Gy, does not correlate with radiation induced alterations in p53 or with alterations in the Gt/S block. However, at 10 Gy, abnormalities in p53 and cell cycle changes were noted for A-T LCL's. Although the results suggest that p53 abnormalities are not central to RDS or the A-T ionizing radiation hypersensitivity disorder, the demonstration of a threshold effect for secondary abnormalities in p53 and cell cycle changes post-irradiation, may help resolve conflicting reports on the involvement of p53 downstream of the central defect in A-T.
Molecular Oncology Program, Cross Cancer Institute, University of Alberta, Edmonton, Canada. labincml@,magi.com
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D001260:Ataxia Telangiectasia / Q000235:genetics*; D002461:Cell Line, Transformed; D004247:DNA / Q000096:biosynthesis / Q000528:radiation effects*; D016193:G1 Phase / Q000528:radiation effects*; D018922:HL-60 Cells / Q000528:radiation effects; D006801:Humans; D010641:Phenotype; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000235:genetics*; D016196:S Phase / Q000528:radiation effects*; D013539:Simian virus 40; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects
D016159:Tumor Suppressor Protein p53; D004247:DNA