Radiation-induced enhanced proliferation of human squamous cancer cells in vitro: a release from inhibition by epidermal growth factor.
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.
Kavanagh
B D
BD
Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0058, USA.
Lin
P S
PS
Chen
P
P
Schmidt-Ullrich
R K
RK
D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000532:radiotherapy; D002452:Cell Count / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D004815:Epidermal Growth Factor; D066246:ErbB Receptors