INHALED ASBESTOS FIBERS INDUCE P53 EXPRESSION IN THE RAT LUNG

Humans and rodents exposed to an aerosol of asbestos fibers develop lu ng injury that can lead to a fibroproliferative response culminating i n excessive scarring and impaired lung function. To define the early e vents that precede asbestos-induced fibrotic lung disease, rats were e xposed to an aerosol of chrysotile asbestos fibers for 5 h. At various times after exposure, the lungs of the asbestos-exposed animals were evaluated immunohistochemically for expression of the p53 tumor suppre ssor protein, a growth regulatory protein. p53 became detectable by im munostaining at the predicted sites of fiber deposition (the bronchiol ar-alveolar duct bifurcations) by 24 h after exposure. The number of c ells positive for p53 immunostaining increased to a maximal level at 8 days after exposure, decreased by 14 days and returned to a low basal level at the 30-day time point. Control groups of rats that were unex posed or exposed to an aerosol of iron beads were negative for p53 imm unostaining throughout the 30-day assessment period. Simultaneous dete ction of the proliferating cell nuclear antigen (PCNA) at the sites of fiber deposition in the asbestos-exposed animals agrees with our prev ious finding that p53 binds and regulates the PCNA promoter.