UVB light induces nuclear factor kappa B (NF kappa B) activity independently from chromosomal DNA damage in cell-free cytosolic extracts.

It has been shown previously that ultraviolet (UV) light (290-320 nm) activates keratinocytes to release proinflammatory cytokines including interleukin (IL)-6. Because the 5' flanking region of the IL-6 gene contains a consensus NF kappa B binding sequence, the effect of UVB light on an NF kappa B-like binding activity was investigated in a human epidermoid carcinoma cell line (A431). Nuclear factor kappa B (NF kappa B) activation in the cytoplasm is known to be due to the dissociation of an inactive NF kappa B-inhibitor of nuclear factor kappa B (I kappa B) complex. Cytosolic extracts from cells harvested shortly after sublethal UVB irradiation showed a UVB dose-dependent increase of NF kappa B binding. The activation was reduced by radical scavenging chemicals, suggesting involvement of reactive oxygen intermediates. NF kappa B activation has been shown previously to be triggered by DNA lesions induced by UV light. To elucidate whether DNA damage is necessary and sufficient to mediate NF kappa B activation crude, cytosolic protein extracts obtained from unirradiated cells were exposed to UVB light. This in vitro UVB treatment led to activation of an NF kappa B-like binding activity, suggesting an additional signaling pathway independent of chromosomal DNA damage or byproducts of DNA damage. The activation process was dependent on the presence of membranes. The data suggest at least an additional signaling pathway for the early UVB response, including a component of the pathway residing at the cell membrane.

Functional aspects of blood platelets in irradiated burros.

In irradiated burros (Equus asinus), a delayed clinical syndrome characterized by a depletion of megakaryocytes and platelets has been observed. To clarify the cause of this syndrome, the functional abilities of platelets in 7 irradiated and 3 control burros were studied in vitro. The irradiated burros were survivors (greater than 18 years) of total-body exposures to near-lethal doses of gamma-radiation. Burro platelet aggregability induced with adenosine diphosphate and thrombin, and with a complex stimulator from burro aortas, was determined by means of a self-calibrating aggregometer. Data indicate that the aggregation responsiveness to adenosine diphosphate and thrombin of platelets from surviving irradiated and unirradiated burros is not defective. An extractible collagen-like stimulator of platelet aggregation was discovered in the aorta of a burro that had survived greater than 24 years after exposure to a total-body dose of 545 roentgens (R) of tantalum-182 gamma-radiation. The platelet-aggregating ability of this stimulator from the vessel wall of the irradiated burro was nearly fourfold greater than that from the aorta of an unirradiated control. Perhaps a delayed radiation effect could be the cause of this vascular agent's high platelet-aggregating ability and could lead to a clinical syndrome marked by depletion of megakaryocytes and platelets.