LOW CONCENTRATIONS OF ACTINOMYCIN-D POTENTIALLY CAUSE THERAPEUTIC DIFFERENTIATION IN HUMAN RHABDOMYOSARCOMA CELL-LINE RD

Neoplastic transformation may be an alteration in the process of cell maturation that leads to an infinite capacity for proliferation. Becau se the cytodestruction caused by most drugs available for cancer chemo therapy is often accompained by significant morbidity and poor respons e, the induction of differentiation has been proposed as art alternati ve approach to conventional anticancer therapy. We used human rhadomyo sarcoma cell line RD to analyze the differentiation process induced by actinomycin D, a drug of choice in the conventional treatment of rhab domyosarcomas. Low concentrations of actinomycin D induced a terminal process of morphological and ultrastructural myogenic differentiation in rhabdomyosarcoma cells, which concluded with cell death. However, t his potential therapeutic effect cannot be considered complete because of the presence of tumoral cells that are heterogeneous with respect to actinomycin D chemosensitivity. This heterogeneity led to the appea rance of foci of resistant cells which, despite their greater degree o f differentiation in comparison with the parental cell fine, escaped f rom terminal myogenic differentiation. This subgroup of tumoral cells may be responsible for the failure of cytotoxic treatment.