Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

We have isolated two Chinese hamster ovary cell lines, designated ADR-4 and ADR-5, which exhibit hypersensitivity to intercalating agents and epipodophyllotoxins. These drugs are thought to exert their cytotoxicity via an interaction with the enzyme topoisomerase II. However, there is no apparent change in the level or catalytic activity of topoisomerase II in the mutant cells. Drug sensitivity does not appear to be due to increased drug transport because accumulation of radiolabeled actinomycin D is similar in mutant and wild-type cells. Both mutant cell lines show enhanced resistance to hydrogen peroxide and to organic peroxides. ADR-4 cells show a degree of temperature sensitivity. ADR-5 cells show mild sensitivity to UV irradiation. Neither cell line shows significant sensitivity to mono- or bifunctional alkylating agents, ionizing radiation, or bleomycin. Cell fusion studies indicate that the phenotype of each mutant cell line is recessive and that the mutants represent two different genetic complementation groups. These studies also indicate that ADR-4 and ADR-5 Adriamycin-sensitive mutant, ADR-1. These results indicate that sensitivity to topoisomerase II inhibitors can result from abnormalities in several genes. These drug-sensitive mutants may be useful for studying the mechanisms of cell killing by topoisomerase II inhibitors, free radicals, and heat.


Journal article


Cancer Res

Publication Date





4526 - 4530


Amsacrine, Animals, Cell Line, Cell Survival, Cricetinae, DNA Topoisomerases, Type II, Dactinomycin, Doxorubicin, Drug Resistance, Etoposide, Female, Mitoxantrone, Mutation, Ovary, Teniposide, Topoisomerase II Inhibitors