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. 1989 May;59(5):722–726. doi: 10.1038/bjc.1989.152

Platinum-dye complexes inhibit repair of potentially lethal damage following bleomycin treatment.

Y Wang 1, T S Herman 1, B A Teicher 1
PMCID: PMC2247223  PMID: 2472165

Abstract

Several new complexes of platinum with positively charged cellular dyes have been synthesised in an effort to find chemotherapeutic drugs with increased antitumour cytotoxicity. As part of this effort, the direct cytotoxicities of some of these complexes as well as their ability to inhibit bleomycin potentially lethal damage repair (PLDR) was studied in vitro in a squamous cancer cell line of human origin (SCC-25). All of the new agents were more cytotoxic against exponentially growing than against plateau phase cell cultures. Exposure of cells to non-lethal drug concentrations for between 1 and 6 h led to measurable inhibition of bleomycin PLDR in the case of each drug tested. In order of decreasing ability to inhibit bleomycin PLDR, Pt(fast black)2, Pt(thioflavin)2 and Pt(thionin)2 were more effective than CDDP, while Pt(methylene blue)2, Pt(Rh-123)2 and Pt(pyronin Y)2 were less effective. The most directly cytotoxic agents were Pt(thioflavin)2, Pt(pyronin Y)2 and Pt(Rh-123)2 which also proved to be the least selectively toxic drugs towards exponential versus plateau phase cells. These results indicate that several of the new platinum complexes may be effective cytotoxic agents as well as effective inhibitors of DNA repair process following exposure of cells to other DNA interactive modalities.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. Crooke S. T., Bradner W. T. Bleomycin, a review. J Med. 1976;7(5):333–428. [PubMed] [Google Scholar]
  3. Einhorn L. H., Donohue J. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med. 1977 Sep;87(3):293–298. doi: 10.7326/0003-4819-87-3-293. [DOI] [PubMed] [Google Scholar]
  4. Ervin T. J., Weichselbaum R., Miller D., Meshad M., Posner M., Fabian R. Treatment of advanced squamous cell carcinoma of the head and neck with cisplatin, bleomycin, and methotrexate (PBM). Cancer Treat Rep. 1981 Sep-Oct;65(9-10):787–791. [PubMed] [Google Scholar]
  5. Frei E., 3rd, Cucchi C. A., Rosowsky A., Tantravahi R., Bernal S., Ervin T. J., Ruprecht R. M., Haseltine W. A. Alkylating agent resistance: in vitro studies with human cell lines. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2158–2162. doi: 10.1073/pnas.82.7.2158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Glick J. H., Marcial V., Richter M., Velez-Garcia E. The adjuvant treatment of inoperable stage III and IV epidermoid carcinoma of the head and neck with platinum and bleomycin infusions prior to definitive radiotherapy: an RTOG pilot study. Cancer. 1980 Nov 1;46(9):1919–1924. doi: 10.1002/1097-0142(19801101)46:9<1919::aid-cncr2820460905>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  7. Hahn G. M., Little J. B. Plateau-phase cultures of mammalian cells: an in vitro model for human cancer. Curr Top Radiat Res Q. 1972 Jul;8(1):39–43. [PubMed] [Google Scholar]
  8. Herman T. S., Teicher B. A., Chan V., Collins L. S., Kaufmann M. E., Loh C. Effect of hyperthermia on the action of cis-diamminedichloroplatinum(II), rhodamine 123(2) [tetrachloroplatinum(II)], rhodamine 123, and potassium tetrachloroplatinate in vitro and in vivo. Cancer Res. 1988 May 1;48(9):2335–2341. [PubMed] [Google Scholar]
  9. Holden S. A., Teicher B. A., Boeheim K., Weichselbaum R. R., Ervin T. J. Platinum complexes inhibit repair of potentially lethal damage following bleomycin treatment. Br J Cancer. 1987 Mar;55(3):245–248. doi: 10.1038/bjc.1987.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hubbard S. P., Chabner B. A., Canellos G. P., Young R. C., DeVita V. T., Jr High dose intravenous bleomycin in the treatment of advanced lymphomas. Eur J Cancer. 1975 Sep;11(9):623–626. doi: 10.1016/0014-2964(75)90096-1. [DOI] [PubMed] [Google Scholar]
  11. Korbelik M., Palcic B., Skarsgard L. D. Bleomycin and misonidazole cytotoxicity. Br J Cancer. 1985 Apr;51(4):499–504. doi: 10.1038/bjc.1985.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LITCHFIELD J. T., Jr, WILCOXON F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther. 1949 Jun;96(2):99–113. [PubMed] [Google Scholar]
  13. O'Hara J. A., Douple E. B., Richmond R. C. Enhancement of radiation-induced cell kill by platinum complexes (carboplatin and iproplatin) in V79 cells. Int J Radiat Oncol Biol Phys. 1986 Aug;12(8):1419–1422. doi: 10.1016/0360-3016(86)90185-9. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Rheinwald J. G., Beckett M. A. Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas. Cancer Res. 1981 May;41(5):1657–1663. [PubMed] [Google Scholar]
  16. Teicher B. A., Cucchi C. A., Lee J. B., Flatow J. L., Rosowsky A., Frei E., 3rd Alkylating agents: in vitro studies of cross-resistance patterns in human cell lines. Cancer Res. 1986 Sep;46(9):4379–4383. [PubMed] [Google Scholar]
  17. Teicher B. A., Holden S. A. Antitumor and radiosensitizing activity of several platinum-(+) dye complexes. Radiat Res. 1987 Jan;109(1):58–67. [PubMed] [Google Scholar]
  18. Teicher B. A., Holden S. A., Jacobs J. L., Abrams M. J., Jones A. G. Intracellular distribution of a platinum-rhodamine 123 complex in cis-platinum sensitive and resistant human squamous carcinoma cell lines. Biochem Pharmacol. 1986 Oct 1;35(19):3365–3369. doi: 10.1016/0006-2952(86)90437-5. [DOI] [PubMed] [Google Scholar]
  19. Teicher B. A., Holden S. A., Kelley M. J., Shea T. C., Cucchi C. A., Rosowsky A., Henner W. D., Frei E., 3rd Characterization of a human squamous carcinoma cell line resistant to cis-diamminedichloroplatinum(II). Cancer Res. 1987 Jan 15;47(2):388–393. [PubMed] [Google Scholar]
  20. Teicher B. A., Rockwell S., Lee J. B. Radiosensitization of EMT6 cells by four platinum complexes. Int J Radiat Oncol Biol Phys. 1985 May;11(5):937–941. doi: 10.1016/0360-3016(85)90116-6. [DOI] [PubMed] [Google Scholar]
  21. Twentyman P. R. Bleomycin--mode of action with particular reference to the cell cycle. Pharmacol Ther. 1983;23(3):417–441. doi: 10.1016/0163-7258(83)90022-0. [DOI] [PubMed] [Google Scholar]
  22. Weichselbaum R. R., Schmit A., Little J. B. Cellular repair factors influencing radiocurability of human malignant tumours. Br J Cancer. 1982 Jan;45(1):10–16. doi: 10.1038/bjc.1982.2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Weichselbaum R. R. The role of DNA repair processes in the response of human tumors to fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 1984 Jul;10(7):1127–1134. doi: 10.1016/0360-3016(84)90187-1. [DOI] [PubMed] [Google Scholar]
  24. Weichselbaum R., Dahlberg W., Little J. B., Ervin T. J., Miller D., Hellman S., Rheinwald J. G. Cellular X-ray repair parameters of early passage squamous cell carcinoma lines derived from patients with known responses to radiotherapy. Br J Cancer. 1984 May;49(5):595–601. doi: 10.1038/bjc.1984.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wittes R., Heller K., Randolph V., Howard J., Vallejo A., Farr H., Harrold C., Gerold F., Shah J., Spiro R. cis-Dichlorodiammineplatinum(II)-based chemotherapy as initial treatment of advanced head and neck cancer. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1533–1538. [PubMed] [Google Scholar]

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