« In vitro » lethal and kinetic effects of 4′-epi-doxorubicin (EPI-DXR) have been established and compared with those of doxorubicin (14-hydroxy-daunorubicin, adriamycin, NSC-123127, DXR). Both drugs show comparable cytotoxicity against a range of murine and human cell lines. Cytotoxicity increases exponentially with drug concentration and with duration of exposure. EPI-DXR like DXR exerts maximal lethal effects during the late S and G2 phases of the cycle in synchronised N1L8 Syrian hamster cells. Flow microfluorimetric data and measurements of mitotic indices provide evidence of population arrest in G2 with both drugs. Responses of various drug-resistant L5178Y cell lines were similar for DXR and EPI-DXR: (i) DXR-resistant cells exhibit complete cross-resistance to EPI-DXR, (ii) vincristine-resistant cells are cross-resistant to DXR and EPI-DXR, and (iii) methotrexate-resistant and 5-fluorouracil-resistant cells show collateral sensitivity to both drugs. These studies emphasise the similarities of DXR and EPI-DXR.
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