Protective action of vitamin C against DNA damage induced by selenium-cisplatin conjugate

• Autorzy: Blasiak J. , Kowalik J.
• Języki publikacji: EN

Abstrakty

EN

Genotoxicity of anticancer drugs is of a special interest due to the risk of inducing sec­ondary malignancies. Vitamin C (ascorbic acid) is a recognized antioxidant and, since hu­man diet can be easily supplemented with vitamin C, it seems reasonable to check whether it can protect against DNA-damaging effects of antitumor drugs. In the present work the ability of vitamin C to modulate cytotoxic and genotoxic effects of a cisplatin analog, con­jugate (NH3)2Pt(SeO3), in terms of cell viability, DNA damage and repair in human lym­phocytes was examined using the trypan blue exclusion test and the alkaline comet assay, respectively. The conjugate evoked a concentration-dependent decrease in the cell viabil­ity, reaching nearly 50% at 250 uM. (NH3)2Pt(SeO3) at 1, 10 and 30 uM caused DNA strand breaks, measured as the increase in the comet tail moment of the lymphocytes. The treated cells were able to recover within a 30-min incubation in a drug-free medium at 37°C. Vitamin C at 10 and 50 uM diminished the extent of DNA damage evoked by (NH3)2Pt(SeO3) but had no effect on the kinetics of DNA repair. The vitamin did not di­rectly inactivate the conjugate. Lymphocytes treated with endonuclease III, which recog­nises oxidised pyrimidines, displayed a greater tail moment than those untreated with the enzyme, suggesting that the damages induced by the drug have, at least in part, an oxida- tive origin. Vitamin C can be considered a potential protective agent against side effects of antitumor drugs, but further research with both normal and cancer cells are needed to clarify this point.

Słowa kluczowe

EN

vitamin C; genotoxicity; anticancer drug; endonuclease III; DNA repair; selenium-cisplatin conjugate; DNA damage; antioxidant; genotoxic effect

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2001
• Tom: 48
• Numer: 1
• Opis fizyczny: p.233-240,fig.

Twórcy

autor

Blasiak J.

• University of Lodz, St.Banacha 12-16, 90-237 Lodz, Poland

autor

Kowalik J.

Bibliografia

• 1.Ferguson, L.R. & Pearson, A.E. (1996) The clinical use of mutagenic anticancer drugs. Mutat. Res. 355, 1-12.
• 2.Eastman, A. & Barry, M.A. (1992) The origins of DNA breaks: A consequence of DNA damage, DNA repair or apoptosis. Cancer Invest. 10, 229-240.
• 3.Fichtinger-Schepman, A.M.J., van Oosterom, A.T. Lohman, P.H.M. & Berends, F. (1987) Cis-diamminedichloroplatinum(II)-induced DNA adducts in peripheral leukocytes from seven cancer patients: Quantitative immunochemical detection of the adduct induction and removal after a single dose of cis-diamminedichloroplatinum(II). Cancer Res. 47, 3000-3004.
• 4.Burger, A.M., Double, J.A. & Newell, D.R. (1997) Inhibition of telomerase activity by cisplatin in human testicular cancer cells. Eur. J. Cancer 33, 638-644.
• 5.Combs, G.F. & Gray, W.P. (1998) Chemopreventive agents: Selenium. Pharmacol. Ther. 79, 179-192.
• 6.Ohkawa, K., Tsukada, Y., Dohzono, H., Koike, K. & Terashima, Y. (1988) The effects of co-administration of selenium and cis-platin (CDDP) on CDDP-induced toxicity and antitumor activity. Br. J. Cancer 58, 38-41.
• 7.Vermeulen, N.P., Baldew, G.S., Los, G., McVie, J.G. & De Goeij, J.J. (1993) Reduction of cisplatin nephrotoxicity by sodium selenite. Lack of interaction at the pharmacokinetic level of both compounds. Drug. Metab. Dispos. 21, 30-36.
• 8.Wachowicz, B. & Olas, B. (1997) Comparative cytotoxicity of cisplatin, sodium selenite and selenium-cisplatin conjugate [(NH3)2Pt(SeO3)]; Changes of blood platelet activation. Gen. Physiol. Biophys. 16, 263-272.
• 9.Blasiak, J., Kowalik, J., Trzeciak, A. & Wojewodzka, M. (1999) Cytotoxicity and DNA damage and repair in human lymphocytes exposed to three anticancer platinum drugs. Neoplasma 46, 61-63.
• 10.Blasiak, J., Kowalik, J., Malecka-Panas, E., Drzewoski, J. & Wojewodzka, M. (2000) DNA damage and repair in human lymphocytes exposed to three anticancer platinum drugs. Teratog, Carcinog, Mutagen. 20, 119-131.
• 11.Panayiotidis, M. & Collins, A.R. (1997) Ex vivo assessment of lymphocyte antioxidant status using the comet assay. Free Radical Res. 27, 533-537.
• 12.Duthie, S.J., Ross, M.A. & Collins, A.R. (1996) Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes. Cancer Res. 56, 1291-1295.
• 13.Blasiak, J. & Kowalik, J. (1999) Protective action of sodium ascorbate against the DNA-damaging effect of malaoxon. Pestic. Biochem. Physiol. 65, 110-118.
• 14.Blasiak, J. & Kowalik, J. (1999) Effect of paraoxon-methyl and parathion-methyl on DNA in human lymphocytes and protective action of vitamin C. Pestic. Sci. 55, 1182-1186.
• 15.Shamberger, R.J. (1984) Genetic toxicology of ascorbic acid. Mutat. Res. 133, 135-159.
• 16.Singh, N.P. (1997) Sodium ascorbate induces DNA single-strand breaks in human cells in vitro. Mutat. Res. 375, 195-203.
• 17.Blasiak, J. & Kowalik, J. (2000) A comparison of the in vitro genotoxicity of tri- and hexavalent chromium. Mutat. Res. 496, 135-145.
• 18.Singh, N.P., McCoy, M.T., Tice, R.R. & Schneider, E.L. (1988) A simple technique for quantification of low levels of DNA damage in individual cells. Exp. Cell Res. 175, 184-191.
• 19.Klaude, M., Eriksson, S., Nygren, J. & Ahnstrom, G. (1996) The comet assay: mechanisms and technical considerations. Mutat. Res. 363, 89-96.
• 20.Barnhart, K.M. & Bowden, G.T. (1985) Cisplatin as an initiating agent in two-stage mouse skin carcinogenesis. Cancer Lett. 29, 101-105.
• 21.Kempf, S.R. & Ivankovic, S. (1986) Carcinogenic effect of cisplatin (cis-diamminedichloroplatinum(II), CDDP) in BD IX rats. J. Cancer Res. Clin. Oncol. 111, 133-136.
• 22.Morin-Faure, J. & Marcollet, M. (1983) Immunocytochemical study of the action of cis-dichlorodiamminoplatinum on the human metaphase chromosome. Eur. J. Cell. Biol. 30, 913-918.
• 23.Bradley, L.J.N., Yarema, K.J., Lippard, S.J. & Essigmann, J.M. (1993) Mutagenicity and genotoxicity of the major DNA adduct of the antitumor drug cis-diamminedichloroplatinum(II). Biochemistry 32, 982-988.
• 24.Baldew, G.S., Mol, J.G.J., de Kanter, F.J.J., van Baar, B., de Goeij, J.J.M. & Vermeulen, N.P.E. (1991) The mechanism of interaction between cisplatin and selenite. Biochem. Pharmacol. 41, 1429-1437.
• 25.Collins, A.R., Duthie, S.J. & Dobson, V.L. (1993) Direct enzymatic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis 14, 1733-1735.
• 26.Doetsch, P.W., Henner, W.D., Cunningham, R.P., Toney, J.H. & Helland, D.E. (1987) A highly conserved endonuclease activity present in Escherichia coli, bovine, and human cells recognizes oxidative DNA damage at sites of pyrimidines. Mol. Cell. Biol. 7, 26-32.
• 27.Weijl, N.I., Hopman, G.D., Wipkink-Bakker, A., Lentjes, E.G., Berger, H.M., Cleton, F.J. & Osanto, S. (1998) Cisplatin combination chemotherapy induces a fall in plasma antioxidants of cancer patients. Ann. Oncol. 9, 1331-1337.