THE MOLECULAR-BASIS FOR CELL-CYCLE DELAYS FOLLOWING IONIZING-RADIATION - A REVIEW

Citation
A. Maity et al., THE MOLECULAR-BASIS FOR CELL-CYCLE DELAYS FOLLOWING IONIZING-RADIATION - A REVIEW, Radiotherapy and oncology, 31(1), 1994, pp. 1-13
Citations number
141
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Oncology,"Radiology,Nuclear Medicine & Medical Imaging
Journal title
ISSN journal
0167-8140
Volume
31
Issue
1
Year of publication
1994
Pages
1 - 13
Database
ISI
SICI code
0167-8140(1994)31:1<1:TMFCDF>2.0.ZU;2-T
Abstract
Exposure of a wide variety of cells to ionizing (X- or gamma-) irradia tion results in a division delay which may have several components inc luding a G(1) block, a G(2) arrest or an S phase delay. The G(1) arres t is absent in many cell lines, and the S phase delay is typically see n following relatively high doses (> 5 Gy). In contrast, the G(2) arre st is seen in virtually all eukaryotic cells and occurs following high and low doses, even under 1 Gy. The mechanism underlying the G(2) arr est may involve suppression of cyclin B1 mRNA and/or protein in some c ell lines and tyrosine phosphorylation of p34(cdc2) in others. Similar mechanisms are likely to be operative in the G(2) arrest induced by v arious chemotherapeutic agents including nitrogen mustard and etoposid e. The upstream signal transduction pathways involved in the G(2) arre st following ionizing radiation remain obscure in mammalian cells; how ever, in the budding yeast the rad9 gene and in the fission yeast the chk1/rad27 gene are involved. There is evidence indicating that shorte ning of the G(2) arrest results in decreased survival which has led to the hypothesis that during this block, cells repair damaged DNA follo wing exposure to genotoxic agents. In cell lines examined to date, wil dtype p53 is required for the G(1) arrest following ionizing radiation . The gadd45 gene may also have a role in this arrest. Elimination of the G(1) arrest leads to no change in survival following radiation in some cell lines and increased radioresistance in others. It has been s uggested that this induction of radioresistance in certain cell lines is due to loss of the ability to undergo apoptosis. Relatively little is known about the mechanism underlying the S phase delay. This delay is due to a depression in the rate of DNA synthesis and has both a slo w and a fast component. In some cells the S phase delay can be abolish ed by staurosporine, suggesting involvement of a protein kinase. Under standing the molecular mechanisms behind these delays may lead to impr ovement in the efficacy of radiotherapy and/or chemotherapy if they ca n be exploited to decrease repair or increase apoptosis following expo sure to these agents.