The effect of anticancer drug vinorelbine on chromatin proteins of alveolar macrophages: comparison with daunomycin

In the present study the effect of daunomycin and vinorelbine on chromatin proteins in alveolar macrophages was investigated and compared. Alveolar macrophages were prepared by lavage and incubated in the absence and presence of various concentrations of the drugs. The histone and non-histone proteins were then extracted and analyzed. The results showed that upon increasing drugs concentration viability of the cells was decreased thus at 80 g/ml, 73% and 50% viability was obtained for daunomycin and vinorelbine respectively. Low concentrations of the drugs had no considerable effect on chromatin proteins content but at higher concentrations the amount of histone H1 was significantly decreased, whereas the content of core histones remained unchanged. The content of H1 subtype, H1o and HMG proteins were also decreased as drugs concentrations increased. Western blot analysis against histone and HMG proteins antisera also confirmed the results. Moreover, staining of the cells with ethidium bromide/acridine orange revealed higher toxicity of vinorelbine compared to daunomycin. From the results it is concluded that vinorelbine exhibits higher affinity to chromatin of alveolar macrophages than daunomycin. Binding of the drugs induce chromatin compaction possibly through histone-histone or histone-DNA cross links thus the proteins were not extractable with manual procedures.