Cytokinetic factors in drug resistance of Lewis lung carcinoma: comparison of cells freshly isolated from tumours with cells from exponential and plateau-phase cultures.
The cytotoxic effects of chemotherapeutic drugs on quiescent and actively proliferating cells of a Lewis lung carcinoma (LLTC) cell line have been examined. The sensitivities of cells in plateau-phase and exponentially growing cultures were compared with those of cells recovered from large subcutaneous tumours both immediately after tumour disaggregation and after one or 4 days in culture. Flow cytometric analysis indicated that when cells freshly prepared from tumours were placed into culture, they underwent extensive recruitment into S-phase. Several drugs were less cytotoxic towards both plateau-phase cultured cells and cells freshly isolated from tumours than they were against exponentially growing cells. These included amsacrine, its 4-methyl-5-(N-methyl)carboxamide derivative CI-921, doxorubicin, and nitrogen mustard. In contrast to these drugs, chlorambucil and plasma from cyclophosphamide-treated mice did not show decreased activity against slowly proliferating cells from cultures or tumours relative to cells in an actively proliferating state. The similar sensitivities of plateau-phase cultured cells and cells taken directly from large growing tumours is direct evidence that plateau-phase cultures are a useful approximation to the state of cytokinetic resistance to chemotherapeutic drugs that prevails in solid tumours, although they may not fully reflect the cytokinetic heterogeneity present in tumours.
Finlay
G J
GJ
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Wilson
W R
WR
Baguley
B C
BC
D000677:Amsacrine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance; D007399:Interphase; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D008938:Mitosis; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D000677:Amsacrine; D004317:Doxorubicin; C042315:asulacrine