A comparison of pathological changes in the mouse lung after dosing with the 3-substituted furans, myomontanone and 3-(N-ethylcarbamoyloxymethyl)furan.

Cellular changes occurring in mouse lung following the administration of myomontanone (MM) were compared with those due to another 3-substituted furan compound, 3-(N-ethylcarbamoyloxymethyl)furan (ECMF). The i.p. administration of lethal doses of these furans resulted in two different forms of lung injury. ECMF was particularly oedemagenic; it resulted in early damage to endothelial cells lining the alveolar capillaries and it also damaged the Clara cells of the terminal bronchioli. Myomontanone was much less oedemagenic and, initially, resulted in minimal cell damage. These minor changes were, however, followed by a delayed but acute injury to the type I pneumocytes, which progressed to elicit the proliferation of type II cells. These two forms of injury probably reflect significant differences in the mechanism of toxicity of the two compounds. The changes following dosing with ECMF resemble those reported after the administration of many other furans, e.g. 4-ipomeanol. The selective injury to type I pneumocytes, observed after MM, has been reported after the administration of many, apparently unrelated, compounds. The late development of MM-induced injury, long after the compound has presumably been cleared from the circulation, may result from the release of reactive metabolites which had previously been bound, reversibly, to cellular macromolecules.