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Comparison of the effects of bleomycin and ionizing radiation in two sublines of murine lymphoma L5178Y

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EN
Abstrakty
EN
We compared the effects of bleomycin (BLM) and ionizing radiation on two sublines of murine lymphoma L5178Y (LY): LY-R, radiation resistant and LY-S, radiation sensitive. This radiosensitivity difference is related to the ability to rejoin DNA double strand breaks. LY-S cells were about two times more sensitive to BLM than LY-R, similarly as in the case of sensitivity to X rays. Since there was no difference in the P-glycoprotein-related drug transport system between the sublines, it could be expected that the enhanced sensitivity of LY-S cells to BLM was caused by the DNA repair defect. Growth disturbances in BLM treated cell populations were proportional to the lethal effect and their duration was observed until elimination of dead cells (3-6 days after 50 ěM BLM, 1 h at 37oC). There was no slow growth phase accompanied by normal viability, as previously described for X-irradiated LY-S cells. Initial DNA damage, estimated with the single cell gel electrophoresis method was linearly related to BLM dose in LY-S cells; in LY-R cells - in the low dose range (up to 10 ěM) - there was more damage than in LY-S cells, however, at higher doses the dose - effect curves became identical. The doseeffect relationship for ă rays was linear and identical in both cell sublines. DNA damage distribution in BLM treated cells was much less uniform as compared to that in irradiated cells and indicated the presence of cells with severely damaged DNA, a feature typical for BLM action in vitro.
Czasopismo
Rocznik
Strony
81--86
Opis fizyczny
Bibliogr. 24 poz., rys.
Twórcy
  • Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland, Tel.: +4822/ 8110736, Fax: +4822/ 8111532
autor
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 5a Pawiƒskiego Str., 02-106 Warsaw, Poland
autor
  • Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland, Tel.: +4822/ 8110736, Fax: +4822/ 8111532
autor
  • Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland, Tel.: +4822/ 8110736, Fax: +4822/ 8111532
Bibliografia
  • 1. Affentranger MI, Burkart W (1995) Resolution of DNA damage at the single-cell level shows largely different actions of X-rays and bleomycin. J Histochem Cytochem 43:229–235
  • 2. Beer JZ, Szumiel I (1994) Slow clones, reduced clonogenicity, and intraclonal recovery in X-irradiated L5178Y-S cell cultures. Radiat Environ Biophys 33:125–139
  • 3. Cheong N, Iliakis G (1997) In vitro rejoining of double strand breaks induced in cellular DNA by bleomycin and restriction endonucleases. Int J Radiat Biol 71:365–375
  • 4. Donner EM, Preston RJ (1996) The relationship between p53 status, DNA repair and chromatid aberration induction in G2 mouse embryo fibroblast cells treated with bleomycin. Carcinogenesis 17:1161–1165
  • 5. Hoffmann GR, Colyer SP, Littlefield LG (1993) Induction of micronuclei by bleomycin in G0 human lymphocytes: I. Doseresponse and distribution. Environ Mol Mutagen 21:130–135
  • 6. Jeggo PA, Kemp LM (1983) X-ray-sensitive mutants of Chinese hamster ovary cell line. Isolation and cross-sensitivity to other DNA-damaging agents. Mutat Res 112:313–327
  • 7. Kruszewski M, Iwanenko T, Bouzyk E, Szumiel I (1999) Chelating of iron and copper alters properties of DNA in L5178Y cells, as revealed by the comet assay. Mutat Res 434:53–60
  • 8. Kruszewski M, Szumiel I (1994) DNA damage induced by hydrogen peroxide treatment at 4°C and 37°C in murine lymphoma L5178Y sublines. Acta Biochim Pol 41:120–121
  • 9. Lloyd RS, Haidle CW, Hewitt RR (1978) Bleomycin-induced alkaline-labile damage and direct strand breakage of PM2 DNA. Cancer Res 38:3191–3196
  • 10. MacLeod RA, Voges M, Bryant PE, Drexler HG (1994) Chromatid aberration dose responses and dispersal in human G2 lymphocytes treated with bleomycin: comparison with equivalent X- irradiation reveals formation of a novel class of heavily damaged cells. Mutat Res 309:73–81
  • 11. Mir LM, Tounekti O, Orlowski S (1996) Bleomycin: revival of an old drug. Gen Pharmacol 27:745–748
  • 12. Neyfakh AA, Dmitrevskaya TV, Serpinskaya AS (1988) The membrane transport system responsible for multidrug resistance is operating in nonresistant cells. Exp Cell Res 178:513–517
  • 13. Nito S (1989) Enhancement of cytogenetic and cytotoxic effects on ultidrug-resistant (MDR) cells by a calcium antagonist (verapamil). Mutat Res 227:73–79
  • 14. Olive PL, Banath JP, Durand RE (1990) Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the “comet” assay. Radiat Res 122:86–94
  • 15. Ostling O, Johanson KJ (1987) Bleomycin, in contrast to gamma irradiation, induces extreme variation of DNA strand breakage from cell to cell. Int J Radiat Biol Relat Stud Phys Chem Med. 52:683–691
  • 16. Povirk LF, Austin MJ (1991) Genotoxicity of bleomycin. Mutat Res 257:127–143
  • 17. Povirk LF, Han YH, Steighner RJ (1989) Structure of bleomycininduced DNA double-strand breaks: predominance of blunt ends and single-base 5’ extensions. Biochemistry 28:5808–5814
  • 18. Povirk LF, Houlgrave CW (1988) Effect of apurinic/apyrimidinic endonucleases and polyamines on DNA treated with bleomycin and neocarzinostatin: specific formation and cleavage of closely opposed lesions in complementary strands. Biochemistry 27:3850–3857
  • 19. Szumiel I (1979) Response of two strains of L5178Y cells to cisdichlorobis(cyclopentylamine)platinum(II). I. Cross-sensitivity to cis- PAD and UV light. Chem-Biol Interact 24:51–72
  • 20. Szumiel I, Kapiszewska M, Kruszewski M, Iwanenko T, Lange CS (1995) Content of iron and copper in the nuclei and induction ofpH 9- labile lesions in L5178Y sublines inversely cross-sensitive to H2O2 and X-rays. Radiat Environ Biophys 34:113–119
  • 21. Vig BK, Lewis R (1978) Genetic toxicology of bleomycin. Mutat Res 55:121–145
  • 22. Wlodek D, Hittelman WN (1987) The repair of double-strand L5178Y-R cells. Radiat Res 112:146–155
  • 23. Wlodek D, Hittelman WN (1988) The relationship of DNA and chromosome damage to survival of synchronized X-irradiated L5178Y cells. I. Initial damage. Radiat Res 115:550–565
  • 24. Wlodek D, Hittelman WN (1988) The relationship of DNA and chromosome damage to survival of synchronized X-irradiated L5178Y cells. II. Repair. Radiat Res 115:566–575
Typ dokumentu
Bibliografia
Identyfikator YADDA
bwmeta1.element.baztech-article-BUJ6-0006-0091
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