Interaction of radiation and AT 1727 in HeLa S-3 cells in culture.
AT 1727, a synthetic analogue of ICRF 159, was reported to have an increased chemotherapeutic index in in vivo leukemic cells. The present cell culture studies were carried out to compare the cytotoxicity of AT 1727 and ICRF 159 in HeLa S-3 cells grown in monolayer and multicellular spheroid systems. The quantitative comparison of cell culture data demonstrated that AT 1727 was more cytotoxic than ICRF 159 at equimolar doses. The increased cytotoxicity at AT 1727 became apparent when the cell survival curves and growth rates of multicellular spheroids were compared at doses above 0.1 mM. When the spheroids were irradiated and exposed to AT 1727 (0.05 mM), there was a pronounced potentiation of radiation effects in the growth rate of spheroids. Similar treatment to ICRF 159 did not show any enhancement of radiation effects. There were also differential effects of AT 1727 and ICRF 159 on the cell cycle progression. AT 1727 causes a G1 block as well as a G2 block in HeLa monolayers, while ICRF 159 only induces G2 block. These cell culture data may be useful for further in vivo tumor studies to determine the therapeutic index of combined radiation and AT 1727.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D010879:Piperazines / Q000494:pharmacology*; D011929:Razoxane / Q000031:analogs & derivatives / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010879:Piperazines; C031186:bimolane; D011929:Razoxane