Decreased repair of radiation-induced DNA double-strand breaks with cellular differentiation.
Although the majority of mammalian cells in situ are terminally differentiated, most DNA repair studies have used proliferating cells. In an attempt to understand better the relationship between differentiation and DNA repair, we have used the murine 3T3-T proadipocyte cell line. In this model system, proliferating (stem) cells undergo growth arrest (GD cells) and subsequently terminally differentiate into adipocytes when exposed to media containing platelet-depleted human plasma. Pulsed-field gel electrophoresis was used to evaluate the induction and repair of DNA double-strand breaks (DSBs) after ionizing radiation. The levels of radiation-induced DSBs in GD and terminally differentiated cells were similar, but in both cases greater than those found in stem cells at each radiation dose tested (0 to 40 Gy); these differences appear to be due to growth arrest in G1 phase. DNA DSBs were repaired with biphasic kinetics for each cell type. For terminally differentiated cells 25% of DNA DSBs remained unrejoined compared with < 10% for GD and stem cells after a repair time of 4 h. These data indicate that terminal differentiation of 3T3-T cells is associated with a reduction in the repair of ionizing radiation-induced DNA DSBs.
Bill
C A
CA
Department of Experimental Radiotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Grochan
B M
BM
Vrdoljak
E
E
Mendoza
E A
EA
Tofilon
P J
PJ
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000528:radiation effects; D000818:Animals; D002250:Carbon Radioisotopes; D002453:Cell Cycle / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects; D002588:Cesium Radioisotopes; D004247:DNA / Q000096:biosynthesis / Q000302:isolation & purification / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D051379:Mice; D013936:Thymidine / Q000378:metabolism
D002250:Carbon Radioisotopes; D002588:Cesium Radioisotopes; D004247:DNA; D013936:Thymidine