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Activation of Phospholipase D Participates in Signal Transduction Pathways Responsive to -Radiation¹

Division of Experimental Carcinogenesis, Department of Radiation Medicine, Georgetown University Medical Center, Washington, D.C. 20007

³ To whom requests for reprints should be addressed.

Early responses of mammalian cells to ionizing radiation include the activation of a protein kinase C implicated in the regulation of gene expression, the stimulation of tyrosine kinase activities, and the enhancement of phosphatidylinositol turnover. In the present report we show that clinically relevant doses of -radiation (2 Gy) stimulate phosphatidylcholine hydrolysis in human squamous carcinoma cells. Radiation induced the accumulation of intracellular [³H]choline and the simultaneous increase in [³H]myristoyl-phosphatidic acid, followed by a small increase in the levels of [³H]myristoyl-diacylglycerol. Furthermore, in the presence of ethanol, -radiation stimulated the appearance of [³²P]phosphatidylethanol, an indicator of phospholipase D transphosphatidylation activity. These data demonstrate for the first time that phospholipase D activation participates in signaling pathways in response to -radiation.

¹ Supported in part by NIH Grant CA 45408.

² M. A. A. and G. O. are fellows of the Spanish Ministry of Education and Fundación Pedro Barrié de la Maza, respectively.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/13/93. Accepted 8/17/93.

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