CHEMICAL MODIFICATIONS ON THE ACYCLIC MOIETY OF 3-(2-HYDROXYETHOXY)-1-ALKOXYPROPYL NUCLEOBASES .2. DIFFERENTIATION AND GROWTH-INHIBITION INRHABDOMYOSARCOMA CELLS AFTER EXPOSURE TO A NOVEL 5-FLUOROURACIL ACYCLONUCLEOSIDE

A series of new 5FU acyclonucleoside analogues has been synthesized an d tested for their in vitro cytotoxicity versus HT-29 colon carcinoma. The only active compound is -hydroxypropoxy)-1-methoxy]propoxy}-5-flu orouracil 14, which is 8-fold less active than 5-fluorouracil. The res t of the newly prepared compounds showed no significant activity We se lected 14 as the drug in the treatment of an human embryonal cell line RD derived from rhabdomyosarcoma. Such treatment caused time-dependen t growth inhibition. Interestingly, RD cells treated with 14 at a conc entration of 90 mu M for 6 days showed phenotypic differentiation, wit h increased expression of desmin, alpha-actinin and tropomyosin. We co nclude that exposure of this human embryonal rhabdomyosarcoma cell lin e to a 90 mu M concentration released the neoplastic cells from their blockade, allowing them to recover normal myogenic development. (C) 19 97 Elsevier Science Ltd.