Microcalorimetric evaluation of the effects of methotrexate and 6-thioguanine on sensitive T-lymphoma cells and on a methotrexate-resistant subline
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Isothermal microcalorimetry was used in order to continuously monitor and quantitatively assess the action of two antineoplastic drugs, methotrexate (MTX) and 6-thioguanine (6-TG), on a human T-lymphoma cell line, CCRF-CEM. The results with MTX were compared with data from experiments with a MTX-resistant subline, CEM/MTX. The slope of the power-time curve after drug injection relative to that obtained during unperturbed growth, was used to construct dose-response curves. The normal cell line was characterized by aD 50 value (i.e., the dose producing half the maximal response) of 0.05 μM for MTX and 0.38 μM for 6-TG. For the MTX-resistant subline theD 50 value was 8 μM of MTX. Comparisons of the continuous power-time curves showed the inhibitory effect of 6-TG to be faster than that of MTX.
Index EntriesMicrocalorimetry on T-lymphoma cells 6-thioguanine methotrexate methotrexate resistant cells dose-response curves
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- 8.Martin, D. S. (1987) Purine and pyrimidine biochemistry, and some relevant clinical and preclinical cancer chemotherapy research, inMetabolism and Action of Anticancer Drugs, Powis, G. and Prough, R. A., eds., Taylor and Francis, London, UK, pp. 91–140.Google Scholar
- 10.Suurkuusk, J. and Wadsö, I. (1982) A multichannel microcalorimeter system.Chem. Scr. 20, 155–163.Google Scholar
- 16.Rosowsky, A., Lazarus, H., Yuan, G. C., Beltz, W. R., Mangini, L., Abelson, H. T., Modest, E. J., and Frei, E., III (1980) Effects of methotrexate esters and other lipophilic antifolates on methotrexate-resistant human leukemic lymphoblasts.Biochem. Pharmacol. 29, 648–652.PubMedCrossRefGoogle Scholar
- 17.Mini, E., Moroson, B. A., Franco, C. T., and Bertino, J. R. (1985) Cytotoxic effects of folate antagonists against methotrexate-resistant human leukemic lymphoblasts CCRF-CEM cell lines.Cancer Res. 5, 325–330.Google Scholar