Relationship between doxorubicin cell sensitivity, drug-induced DNA double-strand breaks, glutathione content and P-glycoprotein in mammalian tumor cells.

We have measured the cytotoxic effect of 1 h exposure to doxorubicin (DOX) on a panel of tumor cell lines. Cellular effects were measured by monolayer colony-forming assay and a colorimetric cytotoxicity assay. As parameters of chemosensitivity we used two different end-points: the dose of DOX that reduces to 50% the number of colonies (ID50) and the dose of DOX that reduces the final optical density to 50% of the control value (IC50). There was a significant correlation between both chemosensitivity indices (r = 0.886, p = 0.0034). DOX-induced DNA double-strand breaks (dsb) were evaluated using pulsed-field gel electrophoresis (PFGE) and compared with cellular effects, P-glycoprotein expression (P-170) and intracellular glutathione (GSH) levels. Our results showed a relationship between the slope of DNA dsb dose-response curves and the percentage of cells that express P-170 (r = -0.957, p = 0.0002). Our study also detects a positive relationship between cellular chemosensitivity parameters and GSH content [ID50 versus GSH (r = 0.794, p = 0.0186), IC50 versus GSH (r = 0.790, p = 0.0198)] in our panel of cell lines.