IONIZING-RADIATION ACTIVATES C-JUN NH2-TERMINAL KINASE (JNK SAPK) VIAA PKC-DEPENDENT PATHWAY IN HUMAN THYROID-CELLS/

Thyroid gland is known to be higher sensitive to carcinogenic effects of external ionizing radiation (IR) than other tissues. To clarify the cell-specific response following irradiation, activations of c-Jun NH 2-terminal kinases (JNKs), which is one of mitogen-activated protein k inases (MAPKs) family members, and extracellular signal-regulated kina se (ERK) were examined in primary cultured human thyroid cells in comp arison with human diploid fibroblast cells, WI-38. Although UV exposur e strikingly induced JNK activity in both cells, the dose-response inc rease following IR exposure was observed in thyroid cells with the max imal JNK activity (3.5 fold induction) obtained at 10 Gy exposure, but no increase in WI-38 cells. The JNK activity was reached a maximum of 2.2 fold induction at 30 min after 5 Gy exposure and then sustained f or at least 12 hr. On the other hand, ERK activity was not stimulated in thyroid cells following irradiation. The effects of 12-O-tetradecan oylphorbol beta-acetate (TPA) mimicked those of radiation on JNK casca de and 1-(5-isoquinolinesulphonyl) -2,5 -dimethylpiperazine 2HCl (H7) and pretreatment with TPA blocked JNK activation following irradiation . Our results demonstrate that IR stimulates JNK activity in cultured human thyroid cells but not in fibroblasts indicating distinct activat ion and regulation mechanisms of JNK cascade. The JNK activation follo wing IR exposure is mediated at least partially through a PKC-dependen t pathway. (C) 1998 Academic Press.