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      Radiation-induced enhanced proliferation of human squamous cancer cells in vitro: a release from inhibition by epidermal growth factor.

      Clinical cancer research : an official journal of the American Association for Cancer Research

      Carcinoma, Squamous Cell, pathology, radiotherapy, Cell Count, drug effects, radiation effects, Cell Cycle, Cell Division, Dose-Response Relationship, Radiation, Epidermal Growth Factor, pharmacology, Humans, Receptor, Epidermal Growth Factor, metabolism, Tumor Cells, Cultured

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          Abstract

          Ionizing radiation is believed to stimulate the repopulation of squamous carcinoma cells that survive the early portion of a fractionated course of radiotherapy. To characterize any intrinsic radiation-induced adaptive response and to examine whether epidermal growth factor (EGF) influences this response, A431 and 183A cells were irradiated with repeated daily exposures of 0.5-0.75 Gy and then grown in monolayer culture for 7 days with or without EGF at a 1 ng/ml concentration. Cell numbers were quantified using a microtiter dye-reduction assay. EGF alone caused approximately 70% and 30% growth inhibition of human SC A431 and 183A cells, respectively. Although radiation alone did not affect proliferative rates in these conditions, radiation eliminated the EGF-related growth inhibition in both cell lines. This effect was dose dependent in single radiation exposure experiments. Cell cycle analyses indicated that EGF initially promoted entry into S-phase 3 days after treatment but caused a G1-S block after 7 days. Treatment with radiation recruited cells into S-phase and G2-M, an effect which was sustained 7 days after treatment, overriding the influence of EGF. Radiation-induced modulation of the response of human squamous carcinoma cells to EGF in vitro after single and repeated radiation exposures suggests a proliferation response that may underlie enhanced repopulation of tumor clonogens in vivo.

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