ASBESTOS INDUCES NUCLEAR FACTOR KAPPA-B (NF-KAPPA-B) DNA-BINDING ACTIVITY AND NF-KAPPA-B-DEPENDENT GENE-EXPRESSION IN TRACHEAL EPITHELIAL-CELLS

Nuclear factor kappa B (NF-kappa B) is a transcription factor regulati ng expression of genes intrinsic to inflammation and cell proliferatio n-features of asbestos-associated diseases. In studies here, crocidoli te asbestos caused protracted and dose-responsive increases in protein s binding to nuclear NF-kappa B-binding DNA elements in hamster trache al epithelial (HTE) cells. This binding was modulated by cellular glut athione levels. Antibodies recognizing p65 and p50 protein members of the NF-kappa B family revealed these proteins in two of the DNA comple xes. Transient transfection assays with a construct containing six NF- kappa B-binding DNA consensus sites linked to a luciferase reporter ge ne indicated that asbestos induced transcriptional activation of NF-ka ppa B-dependent genes, an observation that was confirmed by Northern b lot analyses for c-myc mRNA levels in HTE cells, Studies suggest that NF-kappa B induction by asbestos is a key event in regulation of multi ple genes involved in the pathogenesis of asbestos-related lung cancer s.