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Effect of N-acetylcysteine on the antiproliferative action of X-rays or bleomycin in cultured human lung tumor cells

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  • Experimental Oncology
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Summary

N-Acetylcysteine is currently being considered as a possible selective protector against pulmonary toxicity resulting from X-rays or chemotherapeutic treatment, but its clinical application await evidence that it does not interfere with the efficient killing of tumor cells. The capacity of N-acetylcysteine to protect against the antitumor activity of X-rays and of bleomycin was evaluated in a clonogenic cell-survival assay using SW-1573 human squamous lung carcinoma cells as a tumor model. Using the highest nontoxic dose of N-acetylcysteine (incubation for 2 days in the continuous presence of 10 mM) no effect on clonogenic cell killing by X-rays or bleomycin treatment could be detected, even though a twofold enhancement of endogenous glutathione was effectuated. Our data thus indicate that clinically relevant concentrations of N-acetylcysteine are incapable of protecting tumor cell against clonogenic killing by X-rays and by bleomycin.

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References

  • Bernard RG, Lucht WD, Niedermeyer ME, Snapper JR, Ogletree ML, Brigham KL (1984) Effect of N-acetylcysteine on the pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function.J Clin Invest 73:1772–1784

    PubMed  Google Scholar 

  • Blank LECM, Haveman J, Zandwijk van N (1987) The radioprotective effect of N-acetylcysteine in thorax irradiation of mice. Radiother Oncol 10:67–69

    PubMed  Google Scholar 

  • Borgstrom L, Kagedal B, Paulsen C (1986) Farmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol 31:217–222

    PubMed  Google Scholar 

  • Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine Anal Biochem 106:207–212

    PubMed  Google Scholar 

  • Hacker MP, Lazo JS, Tritton THR (eds) (1988) Organ-directed toxicities of anticancer drugs. Proc 1st Int Symp Organ-directed toxicities of anticancer drugs, Burlington, VT, USA. Martinus Nijhoff, The Hague

    Google Scholar 

  • Jamieson DD, Kerr DR, Unsworth I (1987) Interaction of N-acetylcysteine and bleomycin on hyperbaric oxygen-induced lung damage in mice. Lung 165:239–247

    PubMed  Google Scholar 

  • Joenje H, Van den Berg J, Van Rijn J (1985) Lack of cross-resistance to X-irradiation in oxygen-resistant mammalian cell lines. J Free Radic Biol Med 1:307–310

    PubMed  Google Scholar 

  • Joenje H, Keizer HG, Gille JJP, Van der Valk P, Van Rijn J (1986) Lack of cross-resistance to X-rays and free radical generating drugs in oxygen-resistant Chinese hamster ovary cells. In: Rotilio G (ed) Superoxide and superoxide dismutase in chemistry, biology and medicine. Elsevier Amsterdam, pp 458–460

    Google Scholar 

  • Johnston RE, Hawkins HC, Wiekel JH Jr (1983) The toxicity of N-acetalcysteine in laboratory animals. Semin Oncol 10, suppl 1:17–24

    PubMed  Google Scholar 

  • Keizer HG, Van Rijn J, Pinedo HM, Joenje H (1988) Effect of endogenous glutathione, superoxide dismutases, catalase, and glutathione peroxidase on Adriamycin tolerance of Chinease hamster ovary cells. Cancer Res 48:4493–4497

    PubMed  Google Scholar 

  • Miller LF, Rumack BH (1983) Clinical safety of high oral doses of N-acetylcysteine. Semin Oncol 10 suppl 1:76–85

    PubMed  Google Scholar 

  • Mitchell JB, Russo A (1987) The role of glutathione in radiation and drug induced cytotoxicity. Br J Cancer 55 suppl 8:96–104

    Google Scholar 

  • Moldeus P, Cotgreave IA, Berggren M (1986) Lung protection by a thiol-containing antioxidant: N-acetylcysteine.Respiration 50, Suppl 1:31–42

    Google Scholar 

  • Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356

    PubMed  Google Scholar 

  • Rumack BH, Koch CG, Amara IA (1981) Acetaminophen overdose. 662 Cases with evaluation of oral acetylcysteine treatment. Arch Int Med 141:380–385

    Article  Google Scholar 

  • Russo A, Carmichael J, Frieldman BS, DeGraff W, Tochner Z, Glatstein E, Mitchell JB (1986) The roles of intracellular glutathion in antineoplastic chemotherapy. Int J Radiat Oncol Biol Phys 12:1347–1354

    PubMed  Google Scholar 

  • Tarbell NJ, Rosenblatt M, Amato DA, Hellman S (1986) The effect of N-acetylcysteine inhalation on the tolerance to thoracic irradiation in mice. Radiother Oncol 7:77–80

    PubMed  Google Scholar 

  • Tietze F (1969) Enzymatic methods for quantitative determination of nanogram amounts of total and oxidized glutathione. Anal Biochem 27:502–522

    PubMed  Google Scholar 

  • Van der Schans GP, Vos O, Roos-Verheij WSD, Lohman PHM (1986) The influence of oxygen on the induction of radiation damage in DNA in mammalian cells after sensitization by intracellular glutathione depletion. Int J Radiat Biol 50:453–465

    Google Scholar 

  • Van der Valk P, Gille JJP, Van der Plas LHW, Jongkind JF, Verkerk A, Konings AWT, Joenje H (1988) Characterization of oxygen tolerant Chinese hamster ovary cells. II. Energy metabolism and antioxidant status. Free Radic Biol Med 4:345–356

    Article  PubMed  Google Scholar 

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Wanamarta, A.H., van Rijn, J., Blank, L.E.C.M. et al. Effect of N-acetylcysteine on the antiproliferative action of X-rays or bleomycin in cultured human lung tumor cells. J Cancer Res Clin Oncol 115, 340–344 (1989). https://doi.org/10.1007/BF00400960

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  • DOI: https://doi.org/10.1007/BF00400960

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