Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Nitroimidazole derivatives exhibited genotoxic effect in different experimental conditions. This study focuses on an evaluation of possible genomic targets, at a chromosomal level, of two 5-nitroimidazoles (ornidazole and metronidazole) using the in vitro human peripheral blood culture as experimental system. We observed that both derivatives showed a decrease in mitotic index (MI) (P < 0.001), an increase in sister chromatid exchanges (SCE) frequency (P < 0.001) and no modifications in cellular proliferation kinetics (CPK). As a null hypothesis we considered the assumption that larger chromosomes should harbor more SCE, which was viewed using a novel sequential G-band (400 band resolution)/SCE technique. The analysis showed highly significant chi square values (P < 0.001), indicating that SCE frequency per chromosome is not proportional to chromosome length. SCE could be considered an instability indicator due to the high correlation between SCEs in certain chromosomal bands and the exposure to nitroimidazole derivatives. Copyright © 2008 John Wiley & Sons, Ltd.

Registro:

Documento: Artículo
Título:Nitroimidazole derivatives: Non-randomness sister chromatid exchanges in human peripheral blood lymphocytes
Autor:Carballo, M.A.; Martinez, R.A.; Mudry, M.D.
Filiación:CIGETOX-Citogenética Humana y Genética Toxicológica, Departamento Bioquímica Clfnica. INFIBIOC, Universi- Dad de Buenos Aires, Junin 956 (1113), Ciudad Autónoma de Buenos Aires, Argentina
Dpto de Filosofia e Ciencias Humanas, Universidade Estadual de Santa Cruz, Brazil
GIBE-Grupo de Investigación en Biología Evolutiva Depto Ecología, Genética y Evolución, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
CIGETOX-Citogenética Humana y Genética Toxicológica, Departamento Bioquímica Clínica, Universidad de Buenos Aires, Junin 956 (1113), Ciudad Autónoma de Buenos Aires, Argentina
Palabras clave:Biomarkers; Chromosomal damage; Genomic instability; Genotoxicity; Nitroimidazoles; biological marker; metronidazole; nitroimidazole derivative; ornidazole; adult; article; blood culture; cell proliferation; chromosome; chromosome band; chromosome damage; chromosome size; controlled study; cytotoxicity; drug exposure; female; genome analysis; genomic instability; genotoxicity; human; human cell; human experiment; in vitro study; male; mitosis index; normal human; peripheral lymphocyte; priority journal; sister chromatid exchange; Biological Markers; Cell Division; Cells, Cultured; Chromosome Banding; Dose-Response Relationship, Drug; Female; Humans; Leukocytes, Mononuclear; Male; Metronidazole; Mitotic Index; Mutagenicity Tests; Mutagens; Nitroimidazoles; Ornidazole; Sister Chromatid Exchange; Young Adult
Año:2009
Volumen:29
Número:3
Página de inicio:248
Página de fin:254
DOI: http://dx.doi.org/10.1002/jat.1403
Título revista:Journal of Applied Toxicology
Título revista abreviado:J. Appl. Toxicol.
ISSN:0260437X
CODEN:JJATD
CAS:metronidazole, 39322-38-8, 443-48-1; ornidazole, 16773-42-5; Biological Markers; Metronidazole, 443-48-1; Mutagens; Nitroimidazoles; Ornidazole, 16773-42-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0260437X_v29_n3_p248_Carballo

Referencias:

  • Avani, G., Rao, M.V., Genotoxic effects in human lymphocytes exposed to arsenic and vitamin A (2007) Toxicol. in Vitro, 21, pp. 626-631
  • Azzalin, C.M., Mucciolo, E., Bertoni, L., Giulotto, E., Fluorescence in situ hybridization with a synthetic (T2AG3)n polynucleotide detects several intrachromosomal telomere-like repeats on human chromosomes (1997) Cytogenet. Cell Genet, 78 (2), pp. 112-115
  • Bakopoulou, A., Mourelatos, D., Tsiftsoglou, A.S., Mioglou, E., Garefis, P., Sister chromatid exchange, chromosomal aberrations and deleys in cell-cycle kinetics in human lymphocytes induced by dental composite resin eluates (2008) Mutat. Res, 649, pp. 79-90
  • Barrios, L., Miro, R., Caballin, M., Fuster, C., Guedea, F., Subias, A., Egozcue, J., Cytogenetic effects of radiotherapy: Breakpoint distribution in induced chromosome aberrations (1989) Cancer Genet. Cytogenet, 41 (1), p. 6170
  • Becker, N., Thorland, E., Denison, S., Phillips, L., Smith, D., Evidence that instability within the FRA3B region extends four megabases (2002) Oncogene, 57, pp. 8713-8722
  • Carballo, M.A., Alvarez, S., Boveris, A., Cellular stress by light and rose bengal in human lymphocytes (1993) Mutat. Res, 288, pp. 215-222
  • Carballo, M.A., Palermo, A., López Nigro, M., Andrioli, N., Vázquez, R., Mudry, M., Mutagenicidad quimica y evaluación de daño potencial mediante Ensayos de Corto Plazo (ECT). (2001) A. Toxicol. Arg, 9 (1), pp. 4-8
  • Carballo, M.A., Palermo, A., Mudry, M., Toxicogenetic evaluation of metronidazole treatment of women infected with Trichomona vaginalis (2004) Ann. Trop. Med. Parasitol, 98 (2), pp. 139-147
  • Corbin, S., Neilly, M., Espinosa 3rd, R., Davis, E., McKeithan, T., Le Beau, M., Identification of unstable sequences within the common fragile site at 3p14.2: Implications for the mechanism of deletions within fragile histidine triad gene/common fragile site at 3p14.2 in tumors (2002) Cancer Res, 62 (12), pp. 3477-3484
  • Cortada, C.M., López Nigro, M., Carballo, M.A., Cytotoxicity and P glycoprotein in treatment with niotroimidazoles (2006) Theoria, 15 (2), pp. 34-40
  • Dayan, J., Crajer, M.C., Deguingaund, S., Mutagenic activity of 4 active- principle forms of pharmaceutical drugs. Comparative study in the Salmonella typhimurium microsome test, and the HGPRT and Na+/K+ ATPase systems in cultured mammalian cells (1982) Mutat. Res, 102, pp. 1-12
  • De Meo, M., Vanelle, P., Bernardi, E., Laget, M., Maldonado, J., Jentzer, O., Crozet, M.P., Dumenil, G., Evaluation on mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives by the Ames test and the SOS chromotest (1992) Environmental and Molecular Mutagenesis, 19, pp. 167-170
  • Dobías, L., Cerna, M., Rossner, P., Sram, R., Genotoxicity and carcinogenicity of metronidazole (1994) Mutat. Res, 317 (3), pp. 177-194
  • Edwards, D.I., Reduction of nitroimidazoles and DNA damage (1986) Biochemcal Pharmacology, 35, pp. 53-58
  • Feng, S., Kong, Z., Wang, X., Peng, P., Zeng, E.Y., Assessing the genotoxicity of imidacloprid and RH-5849 in human peripheral blood lymphocytes in vitro with comet assay and cytogenetic tests (2005) Ecotox. Environ. Safety, 61, pp. 239-246
  • Gaddini, L., Pelliccia, F., Limongi, M., Rocchi, A., Study of the relationships between common fragile sites, chromosome breakages and sister chromatid exchanges (1995) Mutagenesis, 10 (3), pp. 257-260
  • Glover, T., Stein, C., Induction of sister chromatid exchanges at common fragile sites (1987) Am. J. Hum. Genet, 41 (5), pp. 882-890
  • Goldman, P., Koch, R.L., Yeung, T.C., Chrystal, E.J., Beaulieu Jr, B.B., McLafferty, M.A., Sudlow, G., Comparing the reduction of nitroimidazoles in bacteria and mammalian tissues and relating it to biological activity (1986) Biochem. Pharmacol, 35, pp. 43-51
  • Guglielmi, G.E., Vogt, T.F., Tice, R.R., Induction of sister chromatid exchanges and inhibition of cellular proliferation in vitro, I. Caffeine (1982) Environm. Mutagen, 4, pp. 191-200
  • Hartley-Asp, B., Metronidazole exhibits no cytogenetic effect in the MN test or in human lymphocytes in vitro (1979) Mutat. Res, 67, pp. 193-196
  • Hirsch, B., Sister chromatid exchanges are preferentially induced at expressed and nonexpressed common fragile sites (1991) Hum. Genet, 87, pp. 302-306
  • Kiuru, A., Lindholm, C., Auvinen, A., Saloma, S., Localization of radiation- induced chromosomal breakpoints along human chromosome 1 using a combination of G-banding and FISH (2000) Int. J. Radiat. Biol, 76 (5), pp. 667-672
  • Kolomietz, E., Meyn, M., Pandita, A., Squire, J., The role of Alu repeat clusters as mediators of recurrent chromosomal aberrations in tumors (2002) Genes Chromosomes Cancer, 35 (2), pp. 97-112
  • LaRusso NF, Tomasz M, Müller M, Lipman R. 1997. Interaction of Metronidazole with nucleic acids in vitro.Mol.Pharmacol 13: 872-882; Latt, S., Allen, J., Bloom, S., Carrano, A., Falke, E., Kram, D., Schneider, E., Wolff, S., Sister-chromatid exchanges: A report of the Gene-Tox Program (1981) Mutat. Res, 87, pp. 17-62
  • Lerda, D., Biaggi Bistoni, M., Peralta, N., Ychari, S., Vazquez, M., Bosio, G., Fumonisins in foods from Cordoba (Argentina), presence and genotoxicity (2005) Food Chem. Toxicol, 43, pp. 690-698
  • Loesche, W.J., Schmidt, E., Smith, B.A., Morrison, E.C., Caffesse, R., Hujoel, P.P., Effects of Metronidazole on periodontal treatment needs (1991) J. Periodontal, 62 (4), pp. 247-257
  • López-Nigro, M., Palermo, A., Mudry, M., Carballo, M.A., Cytogenetic evaluation of two nitroimidazole derivatives (2003) Toxicol. in Vitro, 17, pp. 35-40
  • Ludlum, D.B., Colinas, R.J., Kirk, M.C., Mehta, J.R., Reaction of reduced metronidazole with guanosine to form an unstable adduct (1988) Carcinogenesis, 9, pp. 593-596
  • Madia, F., Gattazzo, C., Wei, M., Fabrizio, P., Burhans, W.C., Weinberger, M., Galbani, A., Longo, V.D., Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system (2008) J. Cell Biol, 180 (1), pp. 67-81
  • Martelli, A., Allavena, A., Robbiano, L., Mattioli, F., Brambilla, G., Comparison of sensitivity of human and rat hepatocytes to the genotoxic effects of metronidazole (1990) Pharmacol. Toxicol, 66, pp. 329-334
  • Martindale, W., Plasmatic concentrations of antiparasitic drugs in man (1993) Extra Pharmacopoeia, pp. 516-523. , Reynolds J ed, The Pharmaceutical Press: London;
  • Matula, T., Validity of in vitro testing (1990) Drug Metab. Rev, 22, pp. 777-787
  • Miller, B.M., Adler, I.D., Suspect spindle poison: Analysis of c-mitotic effect in mouse bone marrow cells (1989) Mutagenesis, 4 (3), pp. 208-215
  • Mudry, M., Carballo, M.A., Labal de Vinuesa, M., González Cid, M., Larripa, I., Mutagenic bioassay of certain pharmacological drugs. III. Metronidazole (MTZ) (1994) Mutat. Res, 305, pp. 127-132
  • Mudry, M., Martinez-Flores, I., Palermo, A., Carballo, M.A., Egozcue, J., García- Caldés, M., Embryolethality induced by metronidazole (MTZ) in Rattus norvegicus (2001) Teratogenesis Carcinogen. Mutag, 21, pp. 197-205
  • Neal, S.B., Probst, G.S., Chemically-induced sister chromatid exchange in vivo in bone marrow of chinese hamster. An evaluation of 24 compounds (1983) Mutat. Res, 113, pp. 33-43
  • Ochi, H., Douglas, H., Sandberg, A., Cytogenetic studies in primary gastric cancer (1986) Cancer Genet. Cytogenet, 22 (4), pp. 295-307
  • http//www.nih.ncbi.gov, On line Mendelian Inheritance in Man. 2003. On line sequenced database of the human genome. Johns Hopkins University, MA. Available at; Palermo, A.M., Reynoso, A.S., López Nigro, M., Mudry, M.D., Carballo, M.A., Teratogenic evaluation of metronidazole and ornidazole using Drosophila melanogaster (2004) Birth Defects Res. (Part A): Clin. Mol. Teratol, 70 (4), pp. 157-162
  • Pekarsky, Y., Zanesi, N., Palamarchuk, A., Huebner, K., Croce, C., FHIT: From gene discovery to cancer treatment and prevention (2002) Lancet Oncol, 3 (12), pp. 748-754
  • Perry, P., Evans, H., Cytological detection of mutagen-carcinogen exposure by sister chromatid exchange (1975) Nature, 258, pp. 121-125
  • Perry, P., Wolf, S., New Giemsa method for differential staining of sister chromatids (1974) Nature, 261, pp. 156-158
  • Raether, W., Hanel, H., Nitroheterocyclic drugs with broad spectrum activity (2003) Parasitol. Res, 90, pp. 19-39
  • Re, J.L., De Méo, M.P., Laget, M., Guiraud, H., Castegnaro, M., Vanelle, P., Duménil, G., Evaluation of the genotoxic activity of metronidazole and dimetridazole in human lymphocytes by the comet assay (1997) Mutat. Res, 375, pp. 147-155
  • Rodriguez Ferreiro, G., Cancino Badías, L., López Nigro, M., Palermo, A., Mudry, M., Prieto Gonzalez, E., Carballo, M.A., DNA single strand breaks in peripheral blood lymphocytes induced by three nitroimidazole derivatives (2002) Toxicol. Lett, 171, pp. 215-222
  • Rudd, M.K., Friedman, C., Pargi, S.S., Linardopoulou, E.V., Hsu, L., Trask, B.J., Elevated rates of Sister Chromatid Exchange at chromosome ends (2007) Plos Genet, 3 (2), pp. 319-323
  • Rustia, M., Shubik, P., Experimental induction of hepatomas mammary tumors and others with metronidazole in non inbred Sas: MRC (W1)BR rats (1979) J. Natl Cancer Inst, 63, pp. 863-868
  • Satanimirovic, Z., Stevanovic, J., Jovanovic, S., Andjelkovic, M., Evaluation of genotoxic effects of Apitol (cymiazole hydrochloride) in vitro by measurement of sister chromatid exchange (2005) Mutat. Res, 588, pp. 152-157
  • Schinkel, A.H., Jonker, J.W., Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: An overview (2003) Adv. Drug Deliv. Rev, 55, pp. 3-29
  • Schmid, O., Speit, G., Genotoxic effects induced by formaldehyde in human blood and implications for the interpretation of biomonitoring studies (2007) Mutagenesis, 22 (1), pp. 69-74
  • Schwartz, S., Astermborski, J., Budacz, A., Boughman, J., Wasserman, S., Cohen, M., Repeated measurement of spontaneous and clastogen induced sister chromatid exchange (1990) Mutat. Res, 234, pp. 51-59
  • Sen, S.K., Kan, H., Wang, J., Lee, J., Wang, H., Callinan, P.A., Dyer, M., Batzer, M.A., Human genomic deletions mediated by recombination between Alu elements (2006) Am. J. Hum. Genet, 79, pp. 41-53
  • Shigemitsu, K., Sekido, Y., Usami, N., Mori, S., Sato, M., Horio, Y., Hasegawa, Y., Shimokata, K., Genetic alteration of the beta-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion (2001) Oncogene, 20 (31), pp. 4249-4257
  • Sutherland, G.R., Richard, G.I., Fragile sites-cytogenetic similarity with molecular diversity (1999) Am. J. Hum. Genet, 64 (2), pp. 354-359
  • Tedeschi, B., Vernole, L., Sanna, M., Nicoletti, B., Population genetics of aphidicolin induced fragile sites (1992) Hum. Genet, 89 (5), pp. 543-547
  • Tossiti, M., Arvelo, F., Analysis of the distribution pattern of sister chromatid exchanges in mitotic chromosomes of human T-lymphocytes (2001) Cytobios, 105 (410), pp. 163-176
  • Tucker, J., Preston, R., Chromosome aberrations, micronuclei, aneuploidy, sister chromatid exchanges and cancer risk assessment (1996) Mutat. Res, 365, pp. 147-159
  • Tucker, J., Auletta, A., Cimino, M., Dearfield, L., Jacobson-Kram, D., Tice, R., Carrano, A., Sister-chromatid exchange: Second report of the Gene-Tox program (1993) Mutat. Res, 297, pp. 101-180
  • Vercauteren, P., Meulepas, E., Vlietinck, R., Cassiman, J., Van den Berghe, H., Non-uniform distribution of sister chromatid exchanges in human lymphocytes (1986) Chromosoma, 93 (3), pp. 197-202
  • Walton, M.I., Workman, P., Nitroimidazole bioreductive metabolism: Quantitation and characterisation of mouse tissue benzimidazole nitro reductase in vivo and in vitro (1987) Biochem. Pharmacol, 36, pp. 883-896
  • Wenger, S., Chemical induction of sister chromatid exchange at fragile sites (1995) Cancer Genet. Cytogenet, 5 (1), pp. 72-74

Citas:

---------- APA ----------
Carballo, M.A., Martinez, R.A. & Mudry, M.D. (2009) . Nitroimidazole derivatives: Non-randomness sister chromatid exchanges in human peripheral blood lymphocytes. Journal of Applied Toxicology, 29(3), 248-254.
http://dx.doi.org/10.1002/jat.1403
---------- CHICAGO ----------
Carballo, M.A., Martinez, R.A., Mudry, M.D. "Nitroimidazole derivatives: Non-randomness sister chromatid exchanges in human peripheral blood lymphocytes" . Journal of Applied Toxicology 29, no. 3 (2009) : 248-254.
http://dx.doi.org/10.1002/jat.1403
---------- MLA ----------
Carballo, M.A., Martinez, R.A., Mudry, M.D. "Nitroimidazole derivatives: Non-randomness sister chromatid exchanges in human peripheral blood lymphocytes" . Journal of Applied Toxicology, vol. 29, no. 3, 2009, pp. 248-254.
http://dx.doi.org/10.1002/jat.1403
---------- VANCOUVER ----------
Carballo, M.A., Martinez, R.A., Mudry, M.D. Nitroimidazole derivatives: Non-randomness sister chromatid exchanges in human peripheral blood lymphocytes. J. Appl. Toxicol. 2009;29(3):248-254.
http://dx.doi.org/10.1002/jat.1403