Induction of doxorubicin resistance in heterogeneous human colon tumor cells by N-methylformamide.
Two clonal subpopulations of cells (termed A and D) obtained originally from a heterogeneous human colon adenocarcinoma were studied in vitro with regard to possible modification of responsivity to graded doses of doxorubicin (ADM) after long-term growth in medium containing the differentiating agent N-methylformamide (NMF). Non-NMF-adapted clone A and D cells exhibited biphasic response curves after exposure to graded doses of ADM (0-1.4 micrograms/ml, 1 hour, 37 degrees C). The inactivation slopes for the initial regions of the survival curves were 0.13 and 0.39 g/ml for clone A and D cells, respectively. NMF-adapted cells, however, exhibited decreased sensitivity to ADM killing as the inactivation slopes for the initial region of the survival curves increased to 0.26 and 0.59 g/ml for clone A and D cells, respectively. The final slopes of the biphasic response curves (doses above about 0.8 micrograms/ml) were not significantly different between clone A and clone D tumor cells in either the non-NMF- or NMF-treated conditions. These data on ADM responses after differentiation induction by NMF indicate that the combination of differentiation-inducing agents with certain chemotherapeutic agents may produce therapeutically undesirable effects and that preclinical data are necessary prior to implementation of possible combined-modality protocols.
D000230:Adenocarcinoma / Q000473:pathology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D004317:Doxorubicin / Q000037:antagonists & inhibitors*; D004351:Drug Resistance; D005559:Formamides / Q000494:pharmacology*; D006801:Humans; D009154:Mutation / Q000187:drug effects
D005559:Formamides; D004317:Doxorubicin; C002950:methylformamide