DIFFERENTIAL RETINOIC ACID RADIOSENSITIZATION OF CERVICAL-CARCINOMA CELL-LINES

The potential of retinoic acid as a radiosensitizer was investigated u sing SiHa and CC-1 human uterine cervical carcinoma cell lines, repres entative of high- and low-grade lesions, respectively, SiHa was signif icantly (P < 0.05) radiosensitized, whereas CC-1 was not, Although 48 h of treatment with 5 mu M 13-cis-retinoic acid prior to irradiation w as sufficient to induce radiosensitization, continuation of treatment after irradiation significantly increased the effect (P < 0.05), Three hypotheses were tested to explain the different responses of the two lines, One hypothesis was that SiHa is more sensitive to retinoic acid than CC-1, Measurement of growth revealed that SiHa was more sensitiv e to growth inhibition by retinoic acid than CC-1, The second hypothes is was that retinoic acid increases the proportion of G(1)-phase cells in SiHa but not in CC-1, This was found not to be true, because a ret inoic acid treatment schedule that induced radiosensitization did not alter cell cycle distribution profiles in the absence of radiation, Th e third hypothesis was that retinoic acid alters the cell cycle respon se of SiHa but not CC-1 to radiation, Postirradiation cell cycle profi les revealed that retinoic acid increased G(1) delay in SiHa, whereas CC-1 exhibited no significant G(1) delay, Both lines exhibited G(2) de lays that were unaffected by retinoic acid, In conclusion, radiosensit ization of SiHa but not CC-1 may be explained by different sensitiviti es to retinoic acid and differences in postirradiation cell cycle resp onses, Radiosensitization at radiation doses used clinically was obser ved when retinoic acid was administered both before and after irradiat ion.