Effect of intratracheally administered anticancer drugs on lung hydroxyproline content

The systemic administration of the anticancer drug bleomycin is associated with the development of lung damage and fibrosis. Intratracheal (i.t.) instillation of bleomycin has often been employed in animal models of this lesion to more rapidly elicit lung damage. However, various drugs and chemicals are known to induce lung damage and fibrosis when given i.t. The results presented here demonstrate that, in addition to bleomycin, the i.t. instillation of dactinomycin, mitomycin c, doxorubicin, and cyclophosphamide resulted in increased lung levels of hydroxyproline, an indicator of fibrosis. In contrast, increases were not seen following i.t. doses of 5-fluorouracil or vincristine, and 1,3-bis(2-chloroethyl)-1-nitrosourea(BCNU) actually decreased lung hydroxyproline content. These findings suggest that i.t. treatments with bleomycin may produce lung damage more representative of anticancer drugs in general than the specific lesion which is produced when bleomycin is administered systemically. The mechanisms underlying i.t. drug-induced increases in lung hydroxyproline are not known, but may be related to the ability of cell-cycle-nonspecific anticancer drugs to directly damage alveolar epithelial cells.