Sodium arsenite enhances AP-1 and NF kappa B DNA binding and induces stress protein expression in precision-cut rat lung slices

Arsenic is a known human carcinogen. These studies were designed to examine the impact of low arsenite concentrations on immediate early gene expressi on in precision-cut rat lung slices. Precision-cut lung slices are a versat ile in-vitro system for toxicity studies, as they preserve the architecture and cellular heterogeneity of the lung. Since 0.1-100 muM arsenite did not compromise slice viability at 4 hours, effects of arsenite on the expressi on of c-jun/AP-1, NF kappaB, HSP 32, HSP 72, HSP 60, and HSP 90 were studie d, using these concentrations of arsenite at 4 h. Nuclear c-jun was increas ed by 10 and 100 muM arsenite, while NF kappaB was not affected. Gel-shift assays indicated that 10 muM arsenite resulted in an enhanced DNA-binding a ctivity of both AP-1 and NF kappaB. Confocal microscopic analysis of AP-1 i ndicated nuclear localization of this transcription factor, mainly in type- II epithelial cells and alveolar macrophages. Nuclear localization of NF ka ppaB was lower than that observed for AP-1, while most of the NF kappaB was localized to cytoplasm of type-II epithelial cells and alveolar macrophage s. HSP 32 was increased by 1.0 and 10 muM arsenite, while HSP 72 was increa sed by only 100 muM arsenite. HSP 60 and HSP 90 were not changed by arsenit e. These studies indicate that noncytotoxic concentrations of arsenite are capable of affecting signal transduction pathways and gene expression in th e lung.