Abstract: |
Apoptosis is induced by radiation, administered at different dose rates of 3-60 Gy/h, in rat embryo cells transfected with a c-myc oncogene (REC:myc(chl)) or with a c-Ha-ras oncogene (REC:ras(chl)). Apoptosis is evaluated in terms of altered morphology, chromatin condensation and DNA fragmentation. The apoptotic dose response of REC:myc(chl) rises steeply at low doses (to about 40% at 5 Gy), and reaches a plateau at high doses (of about 60% at 15 Gy). In comparison with REC:myc(chI), the REC:ras(chI) is much less susceptible, with a maximum apoptotic fraction of about 10%. Interestingly, radiation-induced apoptosis is nearly dose-rate independent. In parallel, we assessed radiation-induced cell-killing as assayed by colony-formation. In contrast to that observed for apoptosis, the dose response of colony-formation is strongly dependent on dose rate. Cell surviving fraction measured at 3 Gy/h decreases exponentially with dose, with REC:myc(chl) exhibiting a steeper slope than REC:ras(chl). Thus, the different low-dose-rate radiosensitivity of the two cell lines may in part be due to their different susceptibility to radiation-induced apoptosis. Taken together, these findings suggest that radiation-induced apoptosis contributes significantly to the initial (shoulder) region of acute dose-rate survival curves of susceptible cells, and may have implications for fractionated and low dose rate radiotherapy. © 1994. |
Keywords: |
controlled study; radiation dose; animal cell; animal; cell death; dna damage; cell survival; apoptosis; embryo; radiotherapy dosage; radiotherapy; cell line; dose-response relationship, radiation; radiation dosage; dna; chromatin; genes, myc; rat; stem cells; rats; genes, ras; cell adhesion; rats, inbred f344; radiation tolerance; gamma radiation; low dose rate; priority journal; article; support, u.s. gov't, p.h.s.; apoptosis radiation
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