Radiation induced G1-block and p53 status in six human cell lines.
Considerable attention has recently been focused on the fact that the tumor suppressor protein p53 is involved in the cellular response to radiation. In its wild-type form the protein appears to control a cell cycle checkpoint, preventing entry into S-phase following DNA damage. A number of authors observed a radiation induced G1-block in cells expressing wild-type p53, but not in p53 mutant cells. We obtained similar results with four human tumour cell lines as well as two strains of human fibroblasts, whose p53 status was ascertained at the protein as well as DNA levels. In addition to cell cycle delays in exponentially growing cell cultures, we have studied the possible role of the p53 in the transition from quiescence to active proliferation. Cells were irradiated after 6 days of serum-starvation and labelled with BrdU at different times after addition of fresh medium. Entry into S-phase was found to be delayed by several hours in the p53 wild-type cells, but no such effect was observed in the p53 mutants. Where a delay occurred, it was roughly proportional to the X-ray dose. Although it remains to be clarified, whether the cells were delayed only in G1 or also in G0, it is interesting to note that entry into S-phase can be delayed by irradiation in a quiescent state immediately before serum-stimulation, provided the cells are wild-type with respect to p53. Certain differences in the cell cycle response of transformed and untransformed cells were noted.
Institut für Medizinische Strahlenbiologie, Universitätsklinikum Essen, Germany.
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F
Zölzer
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S
Hillebrandt
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C
Streffer
D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000528:radiation effects; D002455:Cell Division / Q000235:genetics / Q000528:radiation effects; D002461:Cell Line, Transformed; D016895:Culture Media, Serum-Free; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D016193:G1 Phase / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011879:Radiotherapy Dosage; D016192:Resting Phase, Cell Cycle / Q000528:radiation effects; D016196:S Phase / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000528:radiation effects*
D000963:Antimetabolites; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D001973:Bromodeoxyuridine