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Genomic instability in blood cells is able to predict the oral cancer risk: an experimental study in rats

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Abstract

This study was undertaken to investigate the genomic instability on blood cells during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis by means of single cell gel (comet) and micronucleus assays. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, genetic damage was found in blood cells as depicted by the mean tail moment and an increase of micronucleated polychromatic erythrocytes. After 12 and 20 weeks treatment, the same picture occurred, being the strong effect observed in the micronucleus induction. These periods correspond to pre-neoplastic lesions and well-differentiated squamous cell carcinomas, respectively. Taken together, our results support the idea that genomic instability on blood cells appears to be associated with the risk and progression of oral cancer, being a reliable tool for detecting early systemic conditions of malignancy.

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References

  • Andersson M, Agurell E, Vaghef H, Bolcsfoldi G, Hellman B (2003) Extended-term cultures of human T-lymphocytes and the comet assay: a useful combination when testing for genotoxicity in vitro? Mutat Res 540:43–55

    PubMed  CAS  Google Scholar 

  • Belien JA, Copper MP, Braakhuis BJ et al (1995) Standardization of counting micronuclei: definition of a protocol to measure genotoxic damage in human exfoliated cells. Carcinogenesis 16:2395–2400. doi:10.1093/carcin/16.10.2395

    Article  PubMed  CAS  Google Scholar 

  • Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S et al (1996) Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res 56:2488–2492

    PubMed  CAS  Google Scholar 

  • Charabi S, Balle V, Charabi B, Berthelsen A, Thomsen J (1997) Squamous cell carcinoma of the oral cavity the results of the surgical and non-surgical therapeutic modalities in a consecutive series of 156 patients treated in Copenhagen county. Acta Otolaryngol Suppl 52:9226–9228

    Google Scholar 

  • Frenzilli G, Betti C, Davini T, Desideri M, Fornai E, Giannessi L et al (1997) Evaluation of DNA damage in leukocytes of ex-smokers by single cell gel electrophoresis. Mutat Res 37:117–123. doi:10.1016/S0027-5107(97)00007-9

    Google Scholar 

  • Hagmar L, Bonassi S, Stomberg U et al (1998) Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res 58:4117–4121

    PubMed  CAS  Google Scholar 

  • Hayashi S, Nonoyama T, Miyajima H (1989) Spontaneous non-thymic cell lymphomasin young Wistar rats. Vet Pathol 26:326–332

    Article  PubMed  CAS  Google Scholar 

  • Herzig M, Christofori G (2002) Recent advances in cancer research, mouse models of tumorigenesis. Biochim Biophys Acta 1602:97–113

    PubMed  CAS  Google Scholar 

  • Limoli CL, Kaplan MI, Phillips JW, Adair GM, Morgan WF (1997) Differential induction of chromosomal instability by DNA strand-breaking agents. Cancer Res 57:4048–4056

    PubMed  CAS  Google Scholar 

  • Maluf SW, Erdtmann B (2001) Genomic instability in Down syndrome and Fanconi anemia assessed by micronucleus analysis and single cell-gel electrophoresis. Cancer Genet Cytogenet 124:71–75. doi:10.1016/S0165-4608(00)00322-8

    Article  PubMed  CAS  Google Scholar 

  • Nagpal JK, Patnaik S, Das BR (2002) Prevalence of high-risk human papilloma virus types and its association with P53 codon 72 polymorphism in tobacco addicted oral squamous cell carcinoma OSCC patients of Eastern India. Int J Cancer 10:649–653

    Article  CAS  Google Scholar 

  • Nakajima M, Kikuchi M, Saeki K, Miyata Y, Terada M, Kishida F et al (1999) Mutagenicity of 4-nitroquinoline 1-oxide in the MutaMouse. Mutat Res 444:321–336

    PubMed  CAS  Google Scholar 

  • Neri M, Fucic A, Knudsen LE et al (2003) Micronuclei frequency in children exposed to environmental mutagens: a review. Mutat Res 544:243–254. doi:10.1016/j.mrrev.2003.06.009

    Article  PubMed  CAS  Google Scholar 

  • Nishimura A (1999) Changes in Bcl-2 and Bax expression in rat tongue during 4-nitroquinoline 1-oxide-induced carcinogenesis. J Dent Res 78:1264–1269

    PubMed  CAS  Google Scholar 

  • Ohne M, Satoh T, Yamada S, Takai H (1985) Experimental tongue carcinoma of rats induced by oral administration of 4-nitroquinoline 1-oxide 4NQO in drinking water. Oral Surg Oral Med Oral Pathol 59:600–607. doi:10.1016/0030-4220(85)90189-6

    Article  PubMed  CAS  Google Scholar 

  • Okazaki Y, Tanaka Y, Tonogi M, Yamane G (2002) Investigation of environmental factors for diagnosing malignant potential in oral epithelial dysplasia. Oral Oncol 38:562–573. doi:10.1016/S1368-8375(01)00119-1

    Article  PubMed  CAS  Google Scholar 

  • 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 112:86–94. doi:10.2307/3577587

    Article  Google Scholar 

  • Palyvoda O, Polańska J, Wygoda A, Rzeszowska-Wolny J (2003) DNA damage and repair in lymphocytes of normal individuals and cancer patients: studies by the comet assay and micronucleus tests. Acta Biochim Pol 50:181–190

    PubMed  CAS  Google Scholar 

  • Rao GV, Kumar GS, Ahuja YR (1997) Single cell gel electrophoresis on peripheral blood leukocytes of patients with oral squamous cell carcinoma. J Oral Pathol Med 26:377–380. doi:10.1111/j.1600-0714.1997.tb00234.x

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro DA, Favero Salvadori DM, da Silva RN, Ribeiro Darros B, Alencar Marques ME (2004) Genomic instability in non-neoplastic oral mucosa cells can predict risk during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Oral Oncol 40:910–915. doi:10.1016/j.oraloncology.2004.04.010

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro DA, Salvadori DM, Marques ME (2005) Abnormal expression of bcl-2 and bax in rat tongue mucosa during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide. Int J Exp Pathol 86:375–381. doi:10.1111/j.0959-9673.2005.00444.x

    Article  PubMed  CAS  Google Scholar 

  • Sarasin A (2003) An overview of the mechanisms of mutagenesis and carcinogenesis. Mutat Res 544:99–106. doi:10.1016/j.mrrev.2003.06.024

    Article  PubMed  CAS  Google Scholar 

  • Stich HF, Parida BB, Brunnemann KD (1992) Localized formation of micronuclei in the oral mucosa and tobacco-specific nitrosamines in the saliva of “reverse” smokers, Khaini-tobacco chewers and gudakhu users. Int J Cancer 21:172–176. doi:10.1002/ijc.2910500203

    Article  Google Scholar 

  • Sugimura T, Terada M, Yokota J, Hirohashi S, Wakabayashi K (1992) Multiple genetic alterations in human carcinogenesis. Environ Health Perspect 98:5–12. doi:10.2307/3431242

    Article  PubMed  CAS  Google Scholar 

  • Sugui MM, Alves de Lima PL, Delmanto RD, da Eira AF, Salvadori DM, Ribeiro LR (2003) Antimutagenic effect of Lentinula edodes (BERK.) Pegler mushroom and possible variation among lineages. Food Chem Toxicol 41:555–560. doi:10.1016/S0278-6915(02)00306-X

    Article  PubMed  CAS  Google Scholar 

  • Tanaka T, Kohno H, Sakata K, Yamada Y, Hirose Y, Sugie S et al (2002) Modifying effects of dietary capsaicin and rotenone on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Carcinogenesis 23:1361–1367. doi:10.1093/carcin/23.8.1361

    Article  PubMed  CAS  Google Scholar 

  • Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H et al (2000) Single cell gel/comet assay. Environ Mol Mutagen 35:206–221. doi:10.1002/(SICI)1098-2280(2000)35:3<206::AID-EM8>3.0.CO;2-J

    Google Scholar 

  • Vered M, Daniel N, Hirshberg A, Dayan D (2003) Histomorphologic and morphometric changes in minor salivary glands of the rat tongue during 4-nitroquinoline 1-oxide-induced carcinogenesis. Oral Oncol 39:491–496. doi:10.1016/S1368-8375(03)00011-3

    Article  PubMed  CAS  Google Scholar 

  • Wu X, Lippman SM, Lee JJ, Zhu Y, Wei V, Thomas M et al (2002) Chromosome instability in lymphocytes: a potential indicator of predisposition to oral premalignant lesions. Cancer Res 62:2813–2818

    PubMed  CAS  Google Scholar 

  • Xi S, Grandis JR (2003) Gene therapy for the treatment of oral squamous cell carcinoma. J Dent Res 82:11–16

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are grateful to Paulo Roberto Cardoso and Maria Luiza Falaguera Ardanaz for their technical assistance. This work was supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant number: 07/01228-4). D.G. Grilli is a recipient CNPq student’s fellowship (PIBIC).

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Authors and Affiliations

  1. Department of Biosciences, Federal University of Sao Paulo, UNIFESP, Av. Ana Costa, 95, Vila Mathias, Santos, SP, 11060-001, Brazil

    Daniel A. Ribeiro & Daniela G. Grilli

  2. Department of Pathology, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, SP, Brazil

    Daisy M. F. Salvadori

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  1. Daniel A. Ribeiro
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  2. Daniela G. Grilli
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  3. Daisy M. F. Salvadori
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Correspondence to Daniel A. Ribeiro.

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Ribeiro, D.A., Grilli, D.G. & Salvadori, D.M.F. Genomic instability in blood cells is able to predict the oral cancer risk: an experimental study in rats. J Mol Hist 39, 481–486 (2008). https://doi.org/10.1007/s10735-008-9187-9

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  • DOI: https://doi.org/10.1007/s10735-008-9187-9

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