Topoisomerase II-mediated DNA damage of episomes in tumor-bearing mice

E B Cullinan, L S Gawron, Y M Rustum, T A Beerman
1990 Cancer Research  
Observations of cells in culture have demonstrated that, for many antitumor agents, topoisomerase II-mediated DNA damage relates to cytotoxicity. However, there is no evidence in tumor-bearing animals to suggest that such agents induce topoisomerase II-mediated damage of DNA in solid tumors or that such damage reflects inhibition of tumor growth. To address this question, a mouse fibroblast cell line neoplastically transformed by an episomal element containing the v-Ha-ras and bovine
more » ... rus genes was utilized to measure topoisomerase II-induced DNA damage and growth inhibition of solid tumors derived from this line. Using the topoisomerase II inhibitor amsacrine, the episomal element was found to be a sensitive indicator of topoisomerase II-mediated damage in vivo. The DNA breaks induced by single i.v. injections of amsacrine were protein linked and occurred preferentially in episomal regulatory regions. A strong correlation between suppression of tumor growth and topoisomerase II-mediated damage of the episome was demonstrated.
pmid:2169334 fatcat:hfjqraohzjh7td6mtg2ozsgxci