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. 1988 Jun;57(6):548–552. doi: 10.1038/bjc.1988.126

An in vitro study comparing the cytotoxicity of three platinum complexes with regard to the effect of thiol depletion.

E Smith 1, A P Brock 1
PMCID: PMC2246451  PMID: 3044430

Abstract

The cytotoxicity of three platinum complexes, cis-diamminedichloroplatinum(II) (cis-platin), cis-dichloro-trans-dihydroxy-cis-bis (isopropylamine) platinum(IV), (CHIP) and diammine (1, 1-cyclobutane-dicarboxylato) platinum(II) (carboplatin) on Chinese Hamster ovary (CHO) and mouse sarcoma RIF-1 cells cultured in vitro has been compared. The tumour cell line was much more sensitive to the cytotoxic action of the three agents compared to the CHO cell line. CHIP and carboplatin gave similar dose-response curves, both being much less toxic than cis-platin. The effect of thiol modification on platinum toxicity was also investigated. Substantial reduction in the intracellular non-protein sulphydryl content markedly enhanced the cytotoxicity of CHIP but had much less effect on carboplatin and cis-platin. Thiol depletion by diethylmaleate had a negligible effect on cis-platin toxicity.

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Selected References

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  1. Andrews P. A., Murphy M. P., Howell S. B. Differential potentiation of alkylating and platinating agent cytotoxicity in human ovarian carcinoma cells by glutathione depletion. Cancer Res. 1985 Dec;45(12 Pt 1):6250–6253. [PubMed] [Google Scholar]
  2. Arrick B. A., Nathan C. F. Glutathione metabolism as a determinant of therapeutic efficacy: a review. Cancer Res. 1984 Oct;44(10):4224–4232. [PubMed] [Google Scholar]
  3. Blatter E. E., Vollano J. F., Krishnan B. S., Dabrowiak J. C. Interaction of the antitumor agents cis,cis,trans-PtIV(NH3)2Cl2(OH)2 and cis,cis,trans-PtIV[(CH3)2CHNH2]2Cl2(OH)2 and their reduction products with PM2 DNA. Biochemistry. 1984 Oct 9;23(21):4817–4820. doi: 10.1021/bi00316a001. [DOI] [PubMed] [Google Scholar]
  4. Bump E. A., Yu N. Y., Brown J. M. Radiosensitization of hypoxic tumor cells by depletion of intracellular glutathione. Science. 1982 Aug 6;217(4559):544–545. doi: 10.1126/science.7089580. [DOI] [PubMed] [Google Scholar]
  5. Butler J., Hoey B. M., Swallow A. J. The radiation chemistry of some platinum-containing radiosensitizers and related compounds. Radiat Res. 1985 Apr;102(1):1–13. [PubMed] [Google Scholar]
  6. CONNORS T. A., JENEY A., JONES M. REDUCTION OF THE TOXICITY OF 'RADIOMIMETIC' ALKYLATING AGENTS IN RATS BY THIOL PRETREATMENT. 3. THE MECHANISM OF THE PROTECTIVE ACTION OF THIOSULPHATE. Biochem Pharmacol. 1964 Dec;13:1545–1550. doi: 10.1016/0006-2952(64)90209-6. [DOI] [PubMed] [Google Scholar]
  7. CONTRACTOR S. F. PROTECTION AGAINST NITROGEN MUSTARD BY CYSTEINE AND RELATED SUBSTANCES, INVESTIGATED USING (3H)METHYL-DI-(2-CHLOROETHYL) AMINE. Biochem Pharmacol. 1963 Aug;12:821–832. doi: 10.1016/0006-2952(63)90112-6. [DOI] [PubMed] [Google Scholar]
  8. Canetta R., Rozencweig M., Carter S. K. Carboplatin: the clinical spectrum to date. Cancer Treat Rev. 1985 Sep;12 (Suppl A):125–136. doi: 10.1016/0305-7372(85)90027-1. [DOI] [PubMed] [Google Scholar]
  9. Connors T. A. Protection against the toxicity of alkylating agents by thiols: the mechanism of protection and its relevance to cancer chemotherapy. A review. Eur J Cancer. 1966 Dec;2(4):293–305. doi: 10.1016/0014-2964(66)90042-9. [DOI] [PubMed] [Google Scholar]
  10. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  11. Edwards P. G., Nias A. H. Cell cycle phase sensitivity to cis-dichloro-bis (isopropylamine) trans-dihydroxy platinum (IV) (CHIP). Cell Tissue Kinet. 1986 Jul;19(4):419–427. doi: 10.1111/j.1365-2184.1986.tb00739.x. [DOI] [PubMed] [Google Scholar]
  12. Eichholtz-Wirth H., Hietel B. The relationship between cisplatin sensitivity and drug uptake into mammalian cells in vitro. Br J Cancer. 1986 Aug;54(2):239–243. doi: 10.1038/bjc.1986.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Filipski J., Kohn K. W., Prather R., Bonner W. M. Thiourea reverses cross-links and restores biological activity in DNA treated with dichlorodiaminoplatinum (II). Science. 1979 Apr 13;204(4389):181–183. doi: 10.1126/science.571145. [DOI] [PubMed] [Google Scholar]
  14. Fraval H. N., Roberts J. J. Excision repair of cis-diamminedichloroplatinum(II)-induced damage to DNA of Chinese hamster cells. Cancer Res. 1979 May;39(5):1793–1797. [PubMed] [Google Scholar]
  15. Gottlieb J. A., Drewinko B. Review of the current clinical status of platinum coordination complexes in cancer chemotherapy. Cancer Chemother Rep. 1975 May-Jun;59(3):621–628. [PubMed] [Google Scholar]
  16. Griffith O. W., Meister A. Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). J Biol Chem. 1979 Aug 25;254(16):7558–7560. [PubMed] [Google Scholar]
  17. Hamilton T. C., Winker M. A., Louie K. G., Batist G., Behrens B. C., Tsuruo T., Grotzinger K. R., McKoy W. M., Young R. C., Ozols R. F. Augmentation of adriamycin, melphalan, and cisplatin cytotoxicity in drug-resistant and -sensitive human ovarian carcinoma cell lines by buthionine sulfoximine mediated glutathione depletion. Biochem Pharmacol. 1985 Jul 15;34(14):2583–2586. doi: 10.1016/0006-2952(85)90551-9. [DOI] [PubMed] [Google Scholar]
  18. Krakoff I. H. Nephrotoxicity of cis-dichlorodiammineplatinum(II). Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1523–1525. [PubMed] [Google Scholar]
  19. Ohnuma T., Arkin H., Holland J. F. Effects of cell density on drug-induced cell kill kinetics in vitro (inoculum effect). Br J Cancer. 1986 Sep;54(3):415–421. doi: 10.1038/bjc.1986.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Post G. B., Keller D. A., Connor K. A., Menzel D. B. Effects of culture conditions on glutathione content in A549 cells. Biochem Biophys Res Commun. 1983 Jul 29;114(2):737–742. doi: 10.1016/0006-291x(83)90842-2. [DOI] [PubMed] [Google Scholar]
  21. Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969 Mar;27(3):502–522. doi: 10.1016/0003-2697(69)90064-5. [DOI] [PubMed] [Google Scholar]
  22. Walker I. G., Smith J. F. Protection of L-cells by thiols against the toxicity of sulfur mustard. Can J Physiol Pharmacol. 1969 Feb;47(2):143–151. doi: 10.1139/y69-025. [DOI] [PubMed] [Google Scholar]
  23. Wong W. S., Tindall V. R., Wagstaff J., Bramwell V., Crowther D. Primary carcinoma of the fallopian tube: favourable response to new chemotherapeutic agent, CHIP. J R Soc Med. 1985 Mar;78(3):203–206. doi: 10.1177/014107688507800306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yagoda A., Watson R. C., Gonzalez-Vitale J. C., Grabstald H., Whitmore W. F. Cis-dichlorodiammineplatinum(II) in advanced bladder cancer. Cancer Treat Rep. 1976 Jul;60(7):917–923. [PubMed] [Google Scholar]
  25. Young R. C., Von Hoff D. D., Gormley P., Makuch R., Cassidy J., Howser D., Bull J. M. cis-Dichlorodiammineplatinum(II) for the treatment of advanced ovarian cancer. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1539–1544. [PubMed] [Google Scholar]
  26. Zwelling L. A., Filipski J., Kohn K. W. Effect of thiourea on survival and DNA cross-link formation in cells treated with platinum(II) complexes, L-phenylalanine mustard, and bis(2-chloroethyl)methylamine. Cancer Res. 1979 Dec;39(12):4989–4995. [PubMed] [Google Scholar]

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