Abstract
The observation that tumors are capable of developing resistance to anticancer agents is a well-established fact in the clinic. In order to explain this phenomenon in the laboratory, fluctuation analysis has been used in a number of studies involving tumor cell lines (1–3), although it was first used by Luria and Delbruck (4) in the study of bacterial cultures. Subsequently, work by Goldie and Coldman (5) using fluctuation analysis focused on the genetic instability of tumor cells as pivotal to the emergence of drug-resistant cells. The hypothesis suggested that a drug-resistant cell emerged from the clonal expansion of spontaneously mutated cells and not from changes in cellular function induced by drugs. The methodology used in fluctuation analysis is described elsewhere (3) and can be used to assess the mutation rate of drug treated tumor cells.
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References
Chen, G., Jaffrezou, J. P., Fleming, W. H., Duran, G. E., and Sikic, B. I. (1994) Prevalence of multidrug resistance related to activation of the mdr1 gene in human sarcoma mutants derived by single step doxorubicin selection. Cancer Res. 54, 4980–4987.
Jaffrezou, J. P., Chen, G., Duran, G. E., Kuhl, J. S., Sikic, B. I. (1994) Mutation rates and mechanisms of resistance to etoposide determined from fluctuation analysis. J. Natl. Cancer Inst. 86, 1152–1158.
Beketic-Oreskovic, L., Duran, G. E., Chen, G., Dumontet, C., Sikic, B. I. (1995) Decreased mutation rate for cellular resistance to doxorubicin and suppression of mdr1 gene activation by the cyclosporin PSC833. J. Natl. Cancer Inst. 87, 1593–1602.
Luria, S. E., and Delbruck, M. (1943) Mutation of bacteria from virus sensitivity to virus resistance. Genetics 28, 491–511.
Goldie, J. H., and Coldman, A. J. (1979) A mathematical model for relating the drug sensitivity of tumours to the spontaneous mutation rate. Cancer Treat Rep. 63, 1727–1733.
Biedler, J. L., and Riehm, H. (1970) Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic and cytogenetic studies. Cancer Res. 30, 1174–1184.
Hong, W. S., Saijo, N., Sasaki, Y., et al. (1988) Establishment and characterisation of cisplatin-resistant sublines of human lung cancer cell lines. Int. J. Cancer 41, 462–467.
Scudiero, D. A., Monks, A., Sausville, B. A. (1998) Cell line designation change: multidrug-resistant cell line in the NCI anticancer screen. J. Natl. Cancer Inst. 90, 862.
O’Connor, P. M., Jackman, J., Bae, I., et al. (1997) Characterisation of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth inhibitory potency of 123 anticancer agents. Cancer Res. 57, 4285–4300.
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© 2004 Humana Press Inc., Totowa, NJ
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Coley, H.M. (2004). Development of Drug-Resistant Models. In: Langdon, S.P. (eds) Cancer Cell Culture. Methods in Molecular Medicine™, vol 88. Humana Press. https://doi.org/10.1385/1-59259-406-9:267
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DOI: https://doi.org/10.1385/1-59259-406-9:267
Publisher Name: Humana Press
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