Pulmonary toxicity of methylcyclopentadienyl manganese tricarbonyl: Nonciliated bronchiolar epithelial (Clara) cell necrosis and alveolar damage in the mouse, rat, and hamster

Abstract

Methylcyclopentadienyl manganese tricarbonyl (MMT) was administered ip to young female BALB c mice (120 mg MMT/kg), S A albino rats (5 mg MMT/kg), or LV 6 LAK Syrian hamsters (180 mg MMT/kg). This administration resulted in lung cell damage followed by cellular proliferation, which was quantified by measuring increases in thymidine incorporation into DNA (mouse, rat, and hamster) and by labeling indices (LI) determined from cell kinetic studies (mouse and rat). Thymidine incorporation into pulmonary DNA was significantly elevated within 1 to 2 days following MMT treatment in all three species, with peak incorporation occurring on Day 2 in the rat and hamster, and Day 4 in the mouse. Both bronchiolar and parenchymal LI were elevated at this time. Alveolar damage and nonciliated bronchiolar epithelial (Clara) cell necrosis were evident within 1 day of injection. This finding was followed by type II epithelial and Clara cell proliferation. Ultrastructurally, in the mouse, mitochondrial swelling and degeneration preceded Clara cell necrosis. Bronchiolar damage was most severe in the mouse, whereas parenchymal damage was most severe in the rat. These results suggest that the mouse, rat, and hamster have different susceptibilities to MMT-induced injury.