Table 1

Topoisomerase II inhibition and growth inhibition of CHO and DZR cells by mitindomide, dexrazoxane (ICRF-187), and ICRF-193

DrugIC50Resistance factor
Topoisomerase II inhibitionCell growth inhibition
Human p170 topoisomerase IICHO nuclear extract topoisomerase IICHODZR
μm
Mitindomide200  ± 50 (5)150  ± 50 (3)69  ± 12 (5)2,100  ± 1,000 (3)30
Dexrazoxane9.3  ± 2.7 (4)6.2  ± 1.81-a 5.8  ± 2.1 (4)2,900  ± 190 (4)500
ICRF-1931-b 0.6N.D.0.0170.318

Topoisomerase II inhibition was measured with a gel assay using catenated kDNA as a substrate as described in Materials and Methods. Cell growth inhibition was measured in 96-well plates using an MTT assay after the cells had been incubated with the drug for 72 hr. Values reported are the means ± standard error; the numbers in parentheses are the number of separate determinations carried out on different days.

    • 1-a The mean ± standard error here is from the nonlinear least-squares fit of the data from a single experiment to a logistic equation.

    • 1-b Data from Refs. 12 and 21.

    • N.D., not determined.