Bleomycin-induced synthesis of type I procollagen by human lung and skin fibroblasts in culture.
Bleomycin is a chemotherapeutic agent sometimes associated with pulmonary fibrosis and skin lesions in patients undergoing treatment. We examined the mechanisms of increased collagen deposition on bleomycin-induced fibrosis by incubating human lung and skin fibroblast cultures with [14C]proline; the synthesis of [14C]hydroxyproline relative to DNA or cell protein was taken as an index of procollagen formation. Procollagen synthesis by lung cells in the presence of 0.1 and 1.0 microgram/ml bleomycin was significantly increased and similar results were obtained with skin fibroblasts. The relative synthesis of genetically distinct types of collagen was measured by isolating the newly synthesized type I and type III procollagens by DEAE-cellulose chromatography. The proportion of type III procollagen of total newly synthesized procollagen in control lung fibroblast cultures was 17.4 +/0 0.6% (mean +/- S.E.) while the corresponding value in cells incubated in 1 microgram/ml bleomycin was 12.5 +/- 0.6% (n = 6, P < 0.01). Similar results were obtained when the ratios of newly synthesized type I and type III collagens were estimated by interrupted polyacrylamide disc gel electrophoresis in sodium dodecyl sulfate after a limited proteolytic digestion with pepsin. The results indicate that the increased procollagen synthesis induced by bleomycin in fibroblast cultures is predominantly directed towards the synthesis of type I procollagen.
D001761:Bleomycin / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D008168:Lung / Q000378:metabolism*; D011347:Procollagen / Q000096:biosynthesis*; D011392:Proline / Q000378:metabolism; D014176:Protein Biosynthesis; D012867:Skin / Q000378:metabolism*; D013268:Stimulation, Chemical
D002250:Carbon Radioisotopes; D011347:Procollagen; D001761:Bleomycin; D004247:DNA; D011392:Proline