SUBLETHAL DAMAGE REPAIR CAPACITY IN CARCINOMA CELL-LINES WITH P53 MUTATIONS

Background. The previous findings that sublethal damage repair (SLDR) capacity varies between carcinoma cell lines and that the inherent rad iosensitivity of these lines tends to be higher in connection with p53 mutations lead us to study the possible role of p53 gene in the regul ation of SLDR. The activation of p53 gene by irradiation is known to c ause 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 carc inoma cell lines was determined in split-dose experiments using a 96-w ell plate clonogenic assay. The SLDR capacity as well as the inherent radiosensitivity were compared with the p53 status of the cells. Resul ts. The SLDR capacity varied markedly also between cell lines of simil ar radiosensitivity, but there was a tendency of the more sensitive ce lls to be more SLDR proficient (r= -.69; p =.0016). The beta-values ob tained from linear quadratic equation correlated well with the observe d amount of SLDR (r=.73; p = .0006). With one exception, those cell li nes having p53 mutations showed higher SLDR than those with no mutatio ns (p =.0017). In many of these cell lines, the mutations caused eithe r 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, h ad two mutation points in different alleles, perhaps having less effec t on the protein function. Conclusion. This extended material confirme d the previous result that the SLDR capacity tends to increase with in creasing radiosensitivity in carcinoma cell lines, A cleat correlation between p53 mutations and SLDR capacity was found. The SLDR depended, however, on loss of normal p53 function, which implies that the p53-m ediated G1 arrest is not as important in this repair process, as would have been expected. (C) 1998 John Wiley & Sons, Inc.