Abstract
Plateau-phase Chinese hamster V79 cells were exposed to various concentrations of adriamycin (0-21 micrograms ml-1) in conditioned medium from plateau-phase cultures (C-med). Cells were plated for colony formation, either immediately after adriamycin treatment or after a 24 h incubation either in fresh medium (F-med) or C-med. A potentiation of cell killing was observed in cells plated 24 h after treatments which was larger for cells incubated in F-med than for cells incubated in C-med. Trypsinization of the cells and replating for 24 h in the same volume of medium (total amounts of cells) but at lower surface density to reduce intercellular contact, did not modify the killing potentiation observed after delayed plating. Four to 6 changes of medium, carried out at 1 h intervals, starting immediately after treatment, led to an elimination of the killing potentiation otherwise found in cells kept after treatment in F-med and resulted in survival levels similar to those of cells plated immediately after treatment. On the other hand, survival levels higher by a factor 1.5 to 10 than those obtained for cells plated immediately after treatment were observed for cells kept in C-med when four medium changes were carried out during the first 5 h of the 6 or 24 h post-treatment period. Incubation with 150 microM beta-arabinofuranosyladenine (araA) for 6 h (C-med) after exposure to adriamycin (4 changes of medium at 1 h intervals) prevented the increase in survival observed after incubation in C-med but also caused an additional potentiation in killing resulting in survival levels lower than those of cells plated immediately after treatment. These results are interpreted as indicating the induction by adriamycin of potentially lethal damage (PLD), sensitive to araA, similar to that observed after exposure to low LET ionizing radiation. Repair and/or fixation of this form of PLD can only be shown if precautions are taken to circumvent toxicity induced by adriamycin released from the cells during the post-treatment time interval, for example, by frequent changes in medium.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barranco S. C. In vitro responses of mammalian cells to drug-induced potentially lethal and sublethal damage. Cancer Treat Rep. 1976 Dec;60(12):1799–1810. [PubMed] [Google Scholar]
- Barranco S. C., Novak J. K. Survival responses of dividing and nondividing mammalian cells after treatment with hydroxyurea, arabinosylcytosine, or adriamycin. Cancer Res. 1974 Jul;34(7):1616–1618. [PubMed] [Google Scholar]
- Barranco S. C., Townsend C. M., Jr Loss in cell killing effectiveness of anticancer drugs in human gastric cancer clones due to recovery from potentially lethal damage in vitro. Cancer Res. 1986 Feb;46(2):623–628. [PubMed] [Google Scholar]
- Chambers S. H., Bleehen N. M., Watson J. V. Effect of cell density on intracellular adriamycin concentration and cytotoxicity in exponential and plateau phase EMT6 cells. Br J Cancer. 1984 Mar;49(3):301–306. doi: 10.1038/bjc.1984.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iliakis G., Bryant P. E., Ngo F. Q. Independent forms of potentially lethal damage fixed in plateau-phase Chinese hamster cells by postirradiation treatment in hypertonic salt solution or araA. Radiat Res. 1985 Dec;104(3):329–345. [PubMed] [Google Scholar]
- Iliakis G. Characterization and properties of repair of potentially lethal damage as measured with the help of beta-arabinofuranosyladenine in plateau-phase EAT cells. Radiat Res. 1981 Apr;86(1):77–90. [PubMed] [Google Scholar]
- Iliakis G. Effects of beta-arabinofuranosyladenine on the growth and repair of potentially lethal damage in Ehrilch ascites tumor cells. Radiat Res. 1980 Sep;83(3):537–552. [PubMed] [Google Scholar]
- Iliakis G. Evidence for the induction of two types of potentially lethal damage after exposure of plateau phase Chinese hamster V79 cells to gamma-rays. Radiat Environ Biophys. 1985;24(3):185–202. doi: 10.1007/BF01209522. [DOI] [PubMed] [Google Scholar]
- Iliakis G., Nusse M., Egner J. Enhancement of adriamycin-induced killing after delayed plating of plateau-phase V79-cells. Br J Cancer. 1986 Aug;54(2):245–249. doi: 10.1038/bjc.1986.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iliakis G., Pohlit W. Quantitative aspects of repair of potentially lethal damage in mammalian cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1979 Dec;36(6):649–658. doi: 10.1080/09553007914551481. [DOI] [PubMed] [Google Scholar]
- Martin W. M., McNally N. J. Cytotoxicity of adriamycin to tumour cells in vivo and in vitro. Br J Cancer. 1980 Dec;42(6):881–889. doi: 10.1038/bjc.1980.336. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller W. E., Rohde H. J., Beyer R., Maidhof A., Lachmann M., Taschner H., Kahn R. K. Mode of action of 9-beta-D-arabinofuranosyladenine on the synthesis of DNA, RNA, and protein in vivo and in vitro. Cancer Res. 1975 Aug;35(8):2160–2168. [PubMed] [Google Scholar]
- Phillips R. A., Tolmach L. J. Repair of potentially lethal damage in x-irradiated HeLa cells. Radiat Res. 1966 Nov;29(3):413–432. [PubMed] [Google Scholar]
- Ray G. R., Hahn G. M., Bagshaw M. A., Kurkjian S. Cell survival and repair of plateau-phase cultures after chemotherapy--relevance to tumor therapy and to the in vitro screening of new agents. Cancer Chemother Rep. 1973 Nov-Dec;57(4):473–475. [PubMed] [Google Scholar]
- Rupniak H. T., Whelan R. D., Hill B. T. Concentration and time-dependent inter-relationships for antitumour drug cytotoxicities against tumour cells in vitro. Int J Cancer. 1983 Jul 15;32(1):7–12. doi: 10.1002/ijc.2910320103. [DOI] [PubMed] [Google Scholar]
- Sutherland R. M., Eddy H. A., Bareham B., Reich K., Vanantwerp D. Resistance to adriamycin in multicellular spheroids. Int J Radiat Oncol Biol Phys. 1979 Aug;5(8):1225–1230. doi: 10.1016/0360-3016(79)90643-6. [DOI] [PubMed] [Google Scholar]
- Triton T. R., Yee G. The anticancer agent adriamycin can be actively cytotoxic without entering cells. Science. 1982 Jul 16;217(4556):248–250. doi: 10.1126/science.7089561. [DOI] [PubMed] [Google Scholar]
- Twentyman P. R., Bleehen N. M. Changes in sensitivity to cytotoxic agents occurring during the life history of monolayer cultures of a mouse tumour cell line. Br J Cancer. 1975 Apr;31(4):417–423. doi: 10.1038/bjc.1975.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
