[
European Worm Meeting,
2006]
?. Aggeliki Pasparaki1 Nektarios Tavernarakis1 and Eleni Tzortzaki2. Bleomycin is an antibiotic drug isolated from a strain of Streptomyces verticillus, which has anticancer properties and acts by induction of DNA strand breaks. Due to its cytotoxic properties, the drug has been used to treat many malignant tumors. Bleomycin is also used to induce interstitial pulmonary fibrosis in rodents. Pulmonary fibrosis is a life-threatening condition of unknown molecular etiology in humans. Pulmonary fibrosis affects the alveolar epithelium, the capillary endothelium and the pulmonary basement membrane, where gas exchange is taking place during respiration, and results in abnormal collagen deposition in these tissues. In C. elegans, respiration is achieved by diffusion of oxygen via the intestinal tract, and trough the aqueous film surrounding the body, resembling gas exchange in lung alveoli.. We are investigating the effects of bleomycin on C. elegans survival and physiology. Exposure of worms to bleomycin results in abnormal locomotion, feeding, egg-laying and morphological defects, and lethality. These phenotypes range in severity in a dose dependent manner. The most severe phenotypes are not reversed after removal of the drug. Interestingly, extended exposure to low doses of bleomycin alters the appearance of the cuticle and hypodermis, indicating that similarly to mammals, bleomycin may affect the collagenous exoskeleton of worms by modifying collagen deposition. Thus, genetic analysis in C. elegans may reveal conserved bleomycin targets relevant to the pathogenesis of pulmonary fibrosis in humans.