Sublethal damage repair capacity in carcinoma cell lines with p53 mutations

✍ Scribed by Kirsi Pekkola-Heino; Kristina Servomaa; Anne Kiuru; Reidar Grenman

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 92 KB
• Volume: 20
• Category: Article
• ISSN: 1043-3074
• DOI: 10.1002/(sici)1097-0347(199807)20:4<298::aid-hed3>3.0.co;2-u

✦ Synopsis

Background. The previous findings that sublethal damage repair (SLDR) capacity varies between carcinoma cell lines and that the inherent radiosensitivity of these lines tends to be higher in connection with p53 mutations lead us to study the possible role of p53 gene in the regulation of SLDR. The activation of p53 gene by irradiation is known to cause changes in cell cycle progression. Thus, p53 status probably has effects on cellular radiosensitivity, theoretically through modulating repair processes.

Methods. The SDLR capacity of 17 head and neck carcinoma cell lines was determined in split-dose experiments using a 96well plate clonogenic assay. The SLDR capacity as well as the inherent radiosensitivity were compared with the p53 status of the cells.

Results. The SLDR capacity varied markedly also between cell lines of similar radiosensitivity, but there was a tendency of the more sensitive cells to be more SLDR proficient (r = -.69; p = .0016). The (␤-values obtained from linear quadratic equation correlated well with the observed amount of SLDR (r = .73; p = .0006). With one exception, those cell lines having p53 mutations showed higher SLDR than those with no mutations (p = .0017). In many of these cell lines, the mutations caused either total loss of the p53 protein or major, probably functional changes in it. The cell line UT-SCC-16A, showing no SLDR in the experiments, had two mutation points in different alleles, perhaps having less effect on the protein function.

Conclusion. This extended material confirmed the previous result that the SLDR capacity tends to increase with increasing radiosensitivity in carcinoma cell lines. A clear correlation between p53 mutations and SLDR capacity was found. The SLDR depended, however, on loss of normal p53 function, which implies that the p53-mediated G1 arrest is not as important in this repair process, as would have been expected.