Early cytotoxic effects of mechlorethamine, a nitrogen mustard, on mammalian airway epithelium

Abstract

The aim of this in vitro study was to characterize the early effects of short-term exposure to low concentrations of mechlorethamine (HN2), a nitrogen mustard, on rabbit tracheal primary cultures. Marked inhibition of cell growth was observed without recovery until 14 days after the treatment with sublethal doses of HN2. Cell detachment associated with rearrangement of the cytoskeletal proteins was also noted as early as 1 hr after treatment. Moreover, cells treated with HN2 at the sublethal dose of 50 μm (LC 10) for 1 hr showed early lipid peroxidation and cellular membrane damage. This was correlated with a significant increase in the activities of antioxidant enzymes associated with an increase in glutathione content. These early events appeared several hours before arrest of the cell cycle progression. On the other hand, long-term treatment with HN2 at a sublethal dose led to modification of cytokeratin expression and appeared to induce squamous metaplasia.