EFFECTS OF IONIZING-RADIATION ON CELL-CYCLE PROGRESSION - A REVIEW

Citation
Ej. Bernhard et al., EFFECTS OF IONIZING-RADIATION ON CELL-CYCLE PROGRESSION - A REVIEW, Radiation and environmental biophysics, 34(2), 1995, pp. 79-83
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biophysics,"Radiology,Nuclear Medicine & Medical Imaging","Environmental Sciences
ISSN journal
0301-634X
Volume
34
Issue
2
Year of publication
1995
Pages
79 - 83
Database
ISI
SICI code
0301-634X(1995)34:2<79:EOIOCP>2.0.ZU;2-R
Abstract
Irradiation of normal eukaryotic cells results in delayed progression through the G1, S, and G2 phases of the cell cycle. The G1 arrest is r egulated by the p53 tumor suppressor gene product. Irradiation results in increased expression of p53, which in turn induces a 21 kDa protei n, WAF1/Cip 1, that inhibits cyclin CDK kinases. S-phase delay is obse rved after relatively high doses of radiation. This delay has both rad iosensitive and radioresistant components, corresponding to inhibition of DNA replicon initiation and DNA chain elongation, respectively. Th e mechanism for this delay is as yet undefined, but the extent of the delay appears to be under genetic control and is sensitive to the kina se inhibitor staurosporine. A delay in G2 has been demonstrated in vir tually all eukaryotic cells examined in response to irradiation. Our s tudies have focused on the mechanisms responsible for this delay. Cycl in B1 and p34(cdc2) are cell cycle control proteins that together form a kinase complex required for passage through G2 and mitosis [22]. Co ntrol of radiation-induced G2 delay is likely therefore to involve mod ulation of cyclin B1/p34(cdc2) activity. We have shown in HeLa cells t hat cyclin B1 expression is decreased in a dose-dependent manner follo wing irradiation. This decrease is controlled at both the level of mRN A and protein accumulation. We have also shown that radiation-sensitiv e rat embryo fibroblast lines (REF) immortalized with v- or c-myc disp lay a minimal G2 delay when compared to radiation resistant cells tran sformed with v-myc + H-ras. These REF lines respond to irradiation wit h a decrease in cyclin B mRNA, which parallels the extent of their res pective G2 delays. The duration of the G2 delay in radiation-resistant REF can be shortened by treatment with low doses of the kinase inhibi tor staurosporine. We have also been able to markedly reduce the radia tion-induced G2 delay in HeLa cells using either staurosporine or caff eine. Attenuation of the G2 delay is accompanied by reversal of the ra diation-induced inhibition of cyclin B mRNA accumulation. The results of these studies are consistent with the hypothesis that reduced expre ssion of cyclin B in response to radiation is in part responsible for the G2 delay. The duration of the G2 delay may also be influenced by t he activation state of the cyclin B/p34(cdc2) complex.