Differential retinoic acid radiosensitization of cervical carcinoma cell lines

Doris M. Benbrook, Jane Shen-Gunther, Evelyn R. Nuñez, Joseph R. Dynlacht

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The potential of retinoic acid as a radiosensitizer was investigated using SiHa and CC-1 human uterine cervical carcinoma cell lines, representative of high- and low-grade lesions, respectively. SiHa was significantly (P < 0.05) radiosensitized, whereas CC-1 was not, although 48 h of treatment with 5 μM 13-cis-retinoic acid prior to irradiation was 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 sensitive to growth inhibition by retinoic acid than CC-1. The second hypothesis was that retinoic acid increases the proportion of G1-phase cells in SiHa but not in CC-1. This was found not to be trite, because a retinoic acid treatment schedule that induced radiosensitization did not alter cell cycle distribution profiles in the absence of radiation. The third hypothesis was that retinoic acid alters the cell cycle response of SiHa but not CC-1 to radiation. Postirradiation cell cycle profiles revealed that retinoic acid increased G, delay in SiHa, whereas CC-1 exhibited no significant G, delay. Both lines exhibited G, delays that were unaffected by retinoic acid. In conclusion, radiosensitization of SiHa but not CC-1 may be explained by different sensitivities to retinoic acid and differences in postirradiation cell cycle responses. Radiosensitization at radiation doses used clinically was observed when retinoic acid was administered both before and after irradiation.

Original languageEnglish (US)
Pages (from-to)939-945
Number of pages7
JournalClinical Cancer Research
Volume3
Issue number6
StatePublished - Jun 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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