Alteration of DNA,RNA and collagen synthesis in lung organ cultures exposed to mercury ions

We have examined the effect of Hg²⁺ ions on DNA, RNA and collagen synthesis in organ cultures of neo-natal rat lungs. These cultures exhibit many biochemical characteristics of lung in vivo and they continue to synthesize macromolecules at increasing rates up to 6 days. When these cultures were exposed to 1.0μM HgC1₂, the synthesis of DNA was stimulated nearly 3-fold after 72 hr of exposure followed by a decline at 120 hr reflecting cumulative cytotoxicity. Higher concentrations were inhibitory at all times. A nearly 3-fold increase in RNA synthesis occurred after 24 hr exposure to 1.0 μM HgC1₂ and at 72 hr the cultures continued to synthesize RNA at rates comparable to control. There was a decrease in RNA synthesis at 120 hr. Increased collagen synthesis was observed at concentrations up to 10 μM and at all times. The maximal increase, 2–3 fold, occurred at 120 hr in cultures exposed to 0.1 M. These studies suggest that Hg²⁺-induced cell injury in lung organ cultures elicits a reparative response characterized by increased collagen synthesis. This is similar to chemically induced tissue-injury in lungs in vivo. The relevance of these data to the mechanism of induced pulmonary fibrosis is discussed. These studies also point to the usefulness of organ cultures for studying pulmonary toxicity of environmental agents.