Digital morphonuclear analyses of sensitive versus resistant neoplastic cells to vinca-alkaloid, alkylating, and intercalating drugs.
We tested 12 resistant cell lines in vitro in order to evaluate common morphonuclear characteristics induced by various cytotoxic drugs on cell lines of different origins. We used the MXT mouse mammary cancer and the neoplastic J82 and T24 human bladder cell lines, whose variants are either sensitive or resistant to a vinca alkaloid derivative (Navelbine, NVB), to an investigational alkylating agent (PE1001), and to Adriamycin (ADR). We tested cell population variants resistant to NVB + PE1001 + ADR. The level of chemoresistance was evaluated by a colorimetric assay assessing the 50% concentration-induced inhibition of cellular growth (IC50) brought about by each drug on the growth of each cell variant under study. We show that resistant neoplastic cell nuclei present common morphonuclear characteristics, independent of cell origin (neoplastic mouse mammary versus human bladder cells) and the drug used (vinca alkaloid, alkylating, and intercalating derivatives). Our results further indicate that the phenotype of resistant versus sensitive cells corresponds to cell nuclei populations with smaller nuclei and less nuclear DNA content and, as a consequence, a chromatin texture showing large pale areas with some hyperchromatic clumps.
Pauwels
O
O
Laboratory of Histology, Faculty of Medicine, Free University of Brussels, Belgium.
Kiss
R
R
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D004317:Doxorubicin / Q000494:pharmacology*; D004342:Drug Hypersensitivity; D004351:Drug Resistance; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D015999:Multivariate Analysis; D009930:Organic Chemicals; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009930:Organic Chemicals; C071459:PE 1001; D014747:Vinblastine; D004317:Doxorubicin; D000077235:Vinorelbine