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Response of Thyroid Follicular Cells to Gamma Irradiation Compared to Proton Irradiation: II. The Role of Connexin 32

L. M. Green, D. T. Tran, D. K. Murray, S. S. Rightnar, S. Todd and G. A. Nelson
Radiation Research
Vol. 158, No. 4 (Oct., 2002), pp. 475-485
Stable URL: http://www.jstor.org/stable/3580790
Page Count: 11
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Response of Thyroid Follicular Cells to Gamma Irradiation Compared to Proton Irradiation: II. The Role of Connexin 32
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Abstract

The objective of this study was to determine whether connexin 32-type gap junctions contribute to the "contact effect" in follicular thyrocytes and whether the response is influenced by radiation quality. Our previous studies demonstrated that early-passage follicular cultures of Fischer rat thyroid cells express functional connexin 32 gap junctions, with later-passage cultures expressing a truncated nonfunctional form of the protein. This model allowed us to assess the role of connexin 32 in radiation responsiveness without relying solely on chemical manipulation of gap junctions. The survival curves generated after γ irradiation revealed that early-passage follicular cultures had significantly lower values of α ($0.04\ {\rm Gy}^{-1}$) than later-passage cultures ($0.11\ {\rm Gy}^{-1}$) (P < 0.0001, n = 12). As an additional way to determine whether connexin 32 was contributing to the difference in survival, cultures were treated with heptanol, resulting in higher α values, with early-passage cultures ($0.10\ {\rm Gy}^{-1}$) nearly equivalent to untreated late-passage cultures ($0.11\ {\rm Gy}^{-1}$) (P > 0.1, n = 9). This strongly suggests that the presence of functional connexin 32-type gap junctions was contributing to radiation resistance in γ-irradiated thyroid follicles. Survival curves from proton-irradiated cultures had α values that were not significantly different whether cells expressed functional connexin 32 ($0.10\ {\rm Gy}^{-1}$), did not express connexin 32 ($0.09\ {\rm Gy}^{-1}$), or were down-regulated (early-passage plus heptanol, $0.09\ {\rm Gy}^{-1}$; late-passage plus heptanol, $0.12\ {\rm Gy}^{-1}$) (P > 0.1, n = 19). Thus, for proton irradiation, the presence of connexin 32-type gap junctional channels did not influence their radiosensitivity. Collectively, the data support the following conclusions. (1) The lower α values from the γ-ray survival curves of the early-passage cultures suggest greater repair efficiency and/or enhanced resistance to radiation-induced damage, coincident with the expression of connexin 32-type gap junctions. (2) The increased sensitivity of FRTL-5 cells to proton irradiation was independent of their ability to communicate through connexin 32 gap junctions. (3) The fact that the β components of the survival curves from both γ rays and proton beams were similar (average $0.022\pm 0.008\ {\rm Gy}^{-2}$, P > 0.1, n = 39) suggests that at higher doses the loss of viability occurs at a relatively constant rate and is independent of radiation quality and the presence of functional gap junctions.

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