Benzamide prevention of ultraviolet radiation-induced transformation as measured by anchorage-independent growth and the absence of correlation with thymidine dimer formation and DNA repair.
Synchronized human fibroblasts were exposed in early S phase to increasing doses of ultraviolet (UV) irradiation in the presence and absence of an antitransforming drug, benzamide. Cellular survival, initial thymidine dimer formation and its repair, and cellular phenotypic transformation were simultaneously monitored in the presence and absence of 1 mM externally added benzamide that reaches 8 to 15 microM intracellular levels. Cellular transformation as measured by an expression of anchorage-independent growth was inhibited by nontoxic doses of benzamide. Antitransforming action of benzamide is confined to low intracellular drug concentrations, which in the case of benzamide is in the 4-9 microM range. Because of the lack of effect of benzamide on the formation of UV-induced thymidine dimers and the specific repair of these dimers, these results suggest that the processes of thymidine dimer formation and its repair are not involved in the mode of action of benzamide that influences the expression of a transformed phenotype with low malignant vigor.
Milo
G E
GE
Department of Physiological Chemistry, Ohio State University, Columbus 43210.
D'Ambrosio
S
S
Kun
E
E
D001549:Benzamides / Q000494:pharmacology*; D002448:Cell Adhesion; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D007399:Interphase; D011740:Pyrimidine Dimers / Q000378:metabolism*; D014466:Ultraviolet Rays
D001549:Benzamides; D011740:Pyrimidine Dimers; C037689:benzamide; D004247:DNA