DIFFERENCES IN RADIATION-INDUCED MICRONUCLEI YIELDS OF HUMAN-CELLS - INFLUENCE OF RAS GENE-EXPRESSION AND PROTEIN LOCALIZATION

Citation
Ac. Miller et al., DIFFERENCES IN RADIATION-INDUCED MICRONUCLEI YIELDS OF HUMAN-CELLS - INFLUENCE OF RAS GENE-EXPRESSION AND PROTEIN LOCALIZATION, International journal of radiation biology, 64(5), 1993, pp. 547-554
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging","Nuclear Sciences & Tecnology
ISSN journal
0955-3002
Volume
64
Issue
5
Year of publication
1993
Pages
547 - 554
Database
ISI
SICI code
0955-3002(1993)64:5<547:DIRMYO>2.0.ZU;2-E
Abstract
Expression of ras has been correlated with increased intrinsic resista nce to ionizing radiation. In this study we show that increased EJras expression in human cells is associated with a decrease in the frequen cy of radiation-induced micronuclei. The experimental system consisted of human osteosarcoma-derived cell lines which quantitatively vary in their EJras expression. There was a dose-dependent relationship betwe en radiation dose and micronuclei formation in all cell lines tested. Human osteosarcoma cells, in which the ras level was undetectable, had the highest frequency of micro-nuclei production at all radiation dos es tested. At 4 Gy the most radioresistant cells exhibited a 41.5 +/- 5% decrease in the production of micronuclei concomitant with high ras expression in comparison with the relatively radiosensitive parental cell line. Cells expressing a low amount of EJras demonstrated a 23 +/ - 3% decrease in micronuclei induction compared with parental cells. T reatment of cells with lovastatin, an inhibitor of ras-encoded p21ras post-translational processing via the mevalonate pathway, markedly dec reased the yield of micronuclei formation in cells transfected with ra s; the drug had no effect on radiation-induced micronuclei formation i n parental cells. The use of the in vitro micronuclei assay has provid ed a convenient way to visualize differences in the genotoxic damage i nduced by ionizing radiation in cells which express different amount o f Ejras. The results indicate that elevation of ras expression in huma n cells can lead to a decrease in the number of radiation-induced micr onuclei formed and that this relationship is dependent on membrane ass ociation of ras-encoded p21.