Peripheral Blood Leukocytes as a Surrogate Marker for Cisplatin Drug Resistance: Studies of Adduct Levels and the Repair Gene ERCC1
Cisplatin and its analogs are potent chemotherapeutic agents in the treatment of ovarian cancer, testicular cancer, and other malignancies. Studies by this group have shown that the level of platinum-DNA adduct formed in leukocyte DNA is directly related to disease response in ovarian cancer (Reed et al, 1987) and testicular cancer (Reed et al, 1988a), and that the level of adduct attained is influenced by the persistence of the adduct in leukocyte precursors in some patients for no less than 28 days (Reed et al, 1986). Because this persistence has been observed in some patients but not in others (Reed et al, 1986), we have been interested in the study of those factors that may influence persistence, and whether these factors are directly related to clinical parameters and/or subcellular parameters of cisplatin drug resistance. We have assessed the relative contribution of clinical parameters to disease response in a cohort of patients with ovarian cancer, and we compare those data to platinum-DNA adduct measurements in leukocyte DNA from these same individuals.
KeywordsToxicity Furnace Graphite Platinum Leukemia
Unable to display preview. Download preview PDF.
- Conover, W.J., 1980, “Practical Non-Parametric Statistics,” 2nd ed. Johns Wiley and Sons, New York.Google Scholar
- Davis, L.G., Dibner, M.D., and Battey, J.F., 1986, “Basic Methods in Molecular Biology,” Elsevier, New York.Google Scholar
- Fairchild, C.R., Ivy, S.P., Rushmore, T., Lee, G., Koop, Goldsmith, M.E., Myers, C.E., Farber, E., and Cowan, K.H., 1987, Carcinogen induced mdr expression is associated with xenobiotic resistance in rat preneo- plastic liver nodules and hepatocellular carcinomas. Proc. Natl. Acad. Sci. USA, 84: 7701.PubMedCrossRefGoogle Scholar
- Flamm, W.H., Birnsteil, M.L., and Walter, P.M.B., 1969, in: “Subcellular Components: Preparation and Fractionation,” G. Birnie and S.M. Fox, eds, Butterworth and Co., Ltd., London.Google Scholar
- Hoeijmakers, J.H.J., 1987, Characterization of genes and proteins involved in excision repair of human cells, J Cell Sci (Suppl 6), 111.Google Scholar
- Reed, E., 1989, Cisplatin. in “Cancer Chemotherapy and Biological Response Modifiers Annual - Volume 11,” H.M. Pinedo, B.A Chabner, and D.L. Longo, eds, Elsevier Science Publishers B.V., Amsterdam, in press.Google Scholar
- Reed, E., Sauerhoff, S., and Poirier, M.C., 1988b, Quantitation of platinum-DNA binding in human tissues following therapeutic levels of drug exposure - A novel use of graphite furnace spectrometry, Atomic Spectroscopy, 9: 93.Google Scholar
- Reed, E., Poirier, M.C., Young, R.C., Ozols, R.F., 1988c, High dose cisplatin in hypertonic salines Toxicity versus therapeutic benefit, in: “Organ Directed Toxicities of Anti-Cancer Drugs,” H.P. Hacker, J.S. Lazo, and T.R. Tritton, eds., Martinus Nijhoff Publishers, Boston.Google Scholar
- Van Duin, M., de Wit, J., Odijk, H., Westerveld, A., Yasui, A., Koken, M.H.M., Hoeijmakers, J.H.J., and Bootsma, D., 1986, Molecular characterization of the human excision repair gene ERCC-1: cDNA cloning and amino acid homology with the yeast DNA repair gene RADIO, Cell, 44: 913.PubMedCrossRefGoogle Scholar