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Epidermal Growth Factor Modifies Cell Cycle Control in A431 Human Squamous Carcinoma Cells Damaged by Ionizing Radiation¹

Life Sciences Division, SRI International, Menlo Park, California 94025 [K. R. L., A. M. K., T. D. G., R. M. S.], and Dionex Corporation, Sunnyvale, California 94088 [W. A. A.]

Epidermal growth factor (EGF) has been shown to radiosensitize A431 and other human squamous carcinoma cells with high numbers of surface EGF receptors. In this study of the mechanistic basis of EGF-induced radiosensitization, both EGF and ionizing radiation caused G₁ phase arrests in cycling A431 cells, but only radiation caused a G₂-M arrest. However, EGF enhanced the magnitude of this G₂-M arrest, suggesting an interaction of signaling pathways involved in cellular responses to EGF and radiation damage. EGF and radiation also uniquely perturbed cyclin A and B₁ mRNA levels during the time of maximum radiation-induced G₂-M arrest. The effects of EGF on G₂-M events probably originated in cells in G₁. It is possible that aberrant EGF signal transduction in human squamous carcinoma cells may be exploited as a novel strategy for radiotherapy.

¹ This work was supported by NIH/National Cancer Institute Grants CA 37618 and CA 20329.

Received 12/ 2/93. Accepted 2/ 4/94.

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