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.
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
G J
GJ
Finlay
W R
WR
Wilson
B C
BC
Baguley
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