Are stromal fibroblasts from cervical tumors suitable to predict normal tissue radiation reaction?

We examined the effect of gamma-irradiation (4 Gy) alone or combined with estrogen (17beta-estradiol 15 microM) treatment on the radiation response of stromal fibroblasts from cervical tumors. The fibroblasts were derived from tumors of 9 younger (<50 years) and 9 older (>50 years) cervical cancer patients. A normal fibroblast GSH+/+ cell strain was used as a reference cell. The end-points examined 2 days after irradiation were cell cycle distribution and apoptosis as measured of the cellular response to gamma-radiation. The response of examined fibroblast groups to gamma-rays alone was comparable but apoptotic death was more marked in fibroblasts derived from the younger patients with TNM 1+2 tumors than from the older ones. There was a considerable estrogen effect on the response to gamma-rays that differed between stromal fibroblasts from the examined age groups and was dependent on the tumor stage. In particular, we found a marked decrease in the number of apoptotic cells and debris after estrogen + irradiation, as compared to irradiation alone, only in younger patients and TNM 1+2 tumors. These results indicate that the response of stromal fibroblasts to gamma-rays to a considerable extent depends on donors age and tumor stage. Since stromal fibroblasts have been used for prediction of normal tissue late effects in patients treated with radiotherapy, we conclude that they may not be an adequate model for this purpose.