Advertisement

Methodology of Genotoxic and Teratogenic Studies in Rats

  • Eyyup RencuzogullariEmail author
  • Muhsin Aydin
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1797)

Abstract

The genotoxicity methods applied to rats are tests that can detect any damage, including changes in the number of chromosomes or in the structure of chromosomes, and nucleotide changes with structural abnormality in the DNA of animal cells. However, the method of teratogenicity is used to detect the effects of chemicals which cause congenital defects in living organisms. This study contains information about the effectiveness, reliability, ways of application, and methodology of genotoxic and teratogenic methods applied in vivo in rats.

Key words

Teratogenicity Genotoxicity Mutagenicity Rats Mouse Rodents 

References

  1. 1.
    Dellarco VL, Mavournin KH, Tice RR (1985) Aneuploidy and health risk assessment: current status and future directions. Environ Mutagen 7:405–424CrossRefPubMedGoogle Scholar
  2. 2.
    Takahashi M, Hasegawa R, Furukawa F et al (1986) Effects of ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide on gastric carcinogenesis in rats after initiation with N-methyl-N-nitro-N-nitrosoguanidine. Jpn J Cancer Res 77:118–124PubMedGoogle Scholar
  3. 3.
    Yavuz Kocaman A, Rencuzogullari E, Ila HB, Topaktas M (2008) The genotoxic effect of potassium metabisulfite using chromosome aberration, sister chromatid exchange, micronucleus tests in human lymphocytes and chromosome aberration test in bone marrow cells of rats. Environ Mol Mutagen 49:276–282CrossRefPubMedGoogle Scholar
  4. 4.
    Albertini RJ, Anderson D, Douglas GR et al (2000) IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety. Mutat Res 463:111–172CrossRefPubMedGoogle Scholar
  5. 5.
    Bonassi S, Znaor A, Norppa H, Hagmar L (2004) Chromosomal aberrations and risk of cancer in humans: an epidemiologic perspective. Cytogenet Genome Res 104:376–382CrossRefPubMedGoogle Scholar
  6. 6.
    Bonassi S, Ugolini D, Kirsch Volders M et al (2005) Human population with cytogenetic biomarkers: review of the literature and future prospectives. Environ Mol Mutagen 45:258–270CrossRefPubMedGoogle Scholar
  7. 7.
    Etebari M, Sajjadi SE, Jafarian Dehkordi A, Nazmakanipour S (2016) Genotoxicity evaluation of hydroalcoholic and aqueous extracts of Dorema aucheri by the comet assay. Adv Biomed Res 5:199. https://doi.org/10.4103/2277-9175.190993 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Topaktas M, Rencuzogullari E (2010) Sitogenetik (Cytogenetic). Nobel, TurkeyGoogle Scholar
  9. 9.
    Alkan FU, Anlas C (2015) Genotoxicity tests and genotoxic poisons. Turkish Clinics J Vet Sci Pharmacol Toxicol-Special Topics 1:69–74Google Scholar
  10. 10.
    Wedebye EB, Dybdahl M, Nikolov NG et al (2015) QSAR screening of 70,983 REACH substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the ChemScreen project. Reprod Toxicol 55:64–72CrossRefPubMedGoogle Scholar
  11. 11.
    Tucker JD, Auletta A, Cimino MC et al (1993) Sister chromatid exchange: second report of the gene-Tox program. Mutat Res 297:101–180CrossRefPubMedGoogle Scholar
  12. 12.
    Carrano AV, Natarajan AT (1988) Consideration for population monitoring using cytogenetic techniques. Mutat Res 204:379–406CrossRefPubMedGoogle Scholar
  13. 13.
    Anderson D (1988) Human biomonitoring. Mutat Res 204:353–541CrossRefGoogle Scholar
  14. 14.
    Hagmar L, Brogger A, Hansteen IL et al (1994) Cancer risk in human predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic Study Group on the Health Risk of Chromosome Damage. Cancer Res 54:2919–2922PubMedGoogle Scholar
  15. 15.
    Heddle JA, Cimino MC, Hayashi M et al (1991) Micronuclei as an index of cytogenetic damage: past, present, and future. Environ Mol Mutagen 18:277–291CrossRefPubMedGoogle Scholar
  16. 16.
    Fenech M (2002) Biomarkers of genetic damage for cancer epidemiology. Toxicology 181:411–416CrossRefPubMedGoogle Scholar
  17. 17.
    OECD (1997) Unscheduled DNA synthesis (UDS) test with mammalian liver cells in vivo. In: Guideline for the testing of chemicals. http://www.oecd-ilibrary.org/docserver/download/9748601e.pdf?expires=1494590875& id=id&accname=guest&checksum=48389350D076A0B07DF98A4073340A1F. Accessed 11 May 2017
  18. 18.
    Maron DM, Ames BN (1983) Revised method for the Salmonella mutagenicity test. Mutat Res 113:173–215CrossRefPubMedGoogle Scholar
  19. 19.
    Yavuz Kocaman A, Rencuzogullari E, Topaktas M (2014) In vitro investigation of the genotoxic and cytotoxic effects of thiacloprid in cultured human peripheral blood lymphocytes. Environ Toxicol 29:631–641CrossRefGoogle Scholar
  20. 20.
    EPA (1996) In vivo sister chromatid exchange assay. In: United States Environmental Protection Agency Health Effects Test Guidelines. https://nepis.epa.gov/Exe. Accessed 11 May 2017
  21. 21.
    OECD (1997). Mammalian bone marrow chromosome aberration test. In: Guideline for the testing of chemicals. http://www.oecd-ilibrary.org/environment/test-no-475-mammalian-bone-marrow-chromosome-aberration-test_9789264071308-en. Accessed 12 Mar 2017
  22. 22.
    OECD (2013) Mammalian erythrocyte micronucleus test. In: Guideline for the testing of chemicals. http://www.oecd.org/env/ehs/testing/draft_tg474_second_commenting_round.pdf. Accessed 11 May 2017
  23. 23.
    Cooper GM, Hausman RE (2004) The cell: a molecular approach. ASM, USAGoogle Scholar
  24. 24.
    Topaktas M, Rencuzogullari E, Ila HB (1996) In vivo chromosomal aberrations in bone marrow cells of rats treated with marshal. Mutat Res 371:259–264CrossRefPubMedGoogle Scholar
  25. 25.
    Becerril C, Ferrero M, Sanz F, Castaño A (1999) Detection of mitomycin C-induced genetic damage in fish cells by use of RAPD. Mutagenesis 14:449–456CrossRefPubMedGoogle Scholar
  26. 26.
    Atienzar FA, Jha AN (2006) The random amplified polymorphic DNA (RAPD) assay and related techniques applied to genotoxicity and carcinogenesis studies: a critical review. Mutat Res 613:76–102CrossRefPubMedGoogle Scholar
  27. 27.
    Bayram S, Genc A, Buyukleyla M, Rencuzogullari E (2016) Genotoxicity and cytotoxicity of copper oxychloride in cultured human lymphocytes using cytogenetic and molecular tests. Cytotechnology 68:2027–2036CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Fairbain DW, Olive PL, O’Neill KL (1995) The comet assay: a comprehensive review. Mutat Res 339:37–59CrossRefGoogle Scholar
  29. 29.
    Wilson JG (1973) Environment and birth defects. By Aston SA, Published: 2014-06-21 https://embryo.asu.edu/pages/environment-and-birth-defects-1973-james-g-wilson. Accessed 14 Mar 2017
  30. 30.
    Shreder OV, Shreder ED, Durnev AD, Seredenin SB (2011) Association of genotoxic and teratogenic effects induced by cyclophosphamide and their modification with afobazole. Gig Sanit 5:64–88Google Scholar
  31. 31.
    el-Ashmawy IM, el-Nahas AF, Bayad AE (2011) Teratogenic and cytogenetic effects of ivermectin and its interaction with P-glycoprotein inhibitor. Res Vet Sci 90:116–123CrossRefPubMedGoogle Scholar
  32. 32.
    Murkunde YV, Sathya TN, Subashini N, Murthy PB (2012) Transplacental genotoxicity evaluation of cypermethrin using alkaline comet assay. Hum Exp Toxicol 31:185–192CrossRefPubMedGoogle Scholar
  33. 33.
    Brown NA, Spielmann H, Bechter R et al (1995) Screening chemicals for reproductive toxicity: the current alternatives. Altern Lab Anim 23:868–882Google Scholar
  34. 34.
    Foote RH, Carney EW (2000) The rabbit as a model for reproductive and developmental toxicity studies. Reprod Toxicol 14:477–493CrossRefPubMedGoogle Scholar
  35. 35.
    Bremer S, Hartung T (2004) The use of embryonic stem cells for regulatory developmental toxicity testing in vitro-the current status of test development. Curr Pharm Des 10:2733–2747CrossRefPubMedGoogle Scholar
  36. 36.
    Mace ML Jr, Daskal Y, Wray W (1978) Scanning-electron microscopy of chromosome aberrations. Mutat Res 52:199–206CrossRefPubMedGoogle Scholar
  37. 37.
    Speit G, Haupter S (1985) On the mechanism of differential giemsa staining of bromodeoxyuridine substituted chromosomes. II. Differences between the demostration of sister chromatid differentiation and replication patterns. Hum Genet 70:126–129CrossRefPubMedGoogle Scholar
  38. 38.
    Rencüzogullari E, Ila HB, Kayraldiz A, Topaktaş M (2001) Chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with sodium metabisulfite, a food preservative. Mutat Res 490:107–112CrossRefPubMedGoogle Scholar
  39. 39.
    Matter B, Schmid W (1971) Trenimon-induced chromosomal damage in bone-marrow cells of six mammalian species, evaluated by the micronucleus test. Mutat Res 12:417–425CrossRefPubMedGoogle Scholar
  40. 40.
    von Ledebur M, Schmid W (1973) The micronucleus test. Methodological aspects. Mutat Res 19:109–117CrossRefGoogle Scholar
  41. 41.
    Schmid W (1975) The micronucleus test. Mutat Res 31:9–15CrossRefPubMedGoogle Scholar
  42. 42.
    Romagna F (1988) Series: current issues in mutagenesis and carcinogenesis. 12. Improved method of preparing bone marrow micronucleus assay slides. Mutat Res 206:307–309CrossRefPubMedGoogle Scholar
  43. 43.
    Heddle JA (1990) Micronuclei in vivo. Prog Clin Biol Res 340:185–194Google Scholar
  44. 44.
    Heddle JA, Fenech M, Hayashi M, MacGregor JT (2011) Reflections on the development of micronucleus assays. Mutagenesis 26:3–10CrossRefPubMedGoogle Scholar
  45. 45.
    Oz Aydin S (2004) RAPD (Rastgele Arttırılmış Polimorfik DNA) belirleyicileri ve bitki sistematiği (RAPD markers and plant systematics). Dumlupınar Universitesi Fen Bilimleri Enstitü Dergisi (Dumlupinar Uni J Natural and Applied Sci) 6:113–130Google Scholar
  46. 46.
    Timocin T, Ila HB (2015) Investigation of flurbiprofen genotoxicity and cytotoxicity in rat bone marrow cells. Drug Chem Toxicol 38:355–360CrossRefPubMedGoogle Scholar
  47. 47.
    Doyle JJ, Doyle JL (1987) A rapid DNA isolation procedure for small quantities of fresh leaf tissue. Phytochem Bull 19:11–15Google Scholar
  48. 48.
    Noel S, Rath SK (2006) Randomly amplified polymorphic DNA as a tool for genotoxicity: an assessment. Toxicol Ind Health 22:267–275CrossRefPubMedGoogle Scholar
  49. 49.
    Atienzar FA, Conradi M, Evenden AJ et al (1999) Qualitative assessment of genotoxicity using random amplified polymorphic DNA: comparison of genomic template stability with key fitness parameters in Daphnia magna exposed to benzo[a]pyrene. Environ Toxicol Chem 18:2275–2282PubMedGoogle Scholar
  50. 50.
    Buyukleyla M (2013) Gida katki maddesi sodyum metabisulfit’in genotoksik etkisinin RAPD-PCR yöntemi ile araştırılması (detection of genotoxic effects of food additive sodium metabisulfite using RAPD/PCR method). Cukurova University Institute of Natural and Applied Science, Department of Biology, Doctorate thesis (Supervisor Topaktas M), p 107Google Scholar
  51. 51.
    Dincer Y, Kankaya S (2010) DNA Hasarının Belirlenmesinde Comet Assay (Comet Assay for determining of DNA damage). J Med Sci 30:1365–1373Google Scholar
  52. 52.
    OECD (2016) In vivo mammalian alkaline Comet Assay. In: Guideline for the testing of chemicals. http://www.oecd-ilibrary.org/docserver/download/9716431e.pdf?expires=1494577986&id=id&accname=guest&checksum=9471A50A37B578F471C06D74E4A7760A. Accessed 11 May 2017
  53. 53.
    Ostling O, Johanson KJ (1984) Microelectrophoretic study of radiation-induced DNA damage in individual mammalian cells. Biochem Biophys Res Commun 123:291–298CrossRefPubMedGoogle Scholar
  54. 54.
    Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191CrossRefPubMedGoogle Scholar
  55. 55.
    Horoz M, Bolukbas C, Bolukbas F et al (2006) Assessment of peripheral DNA damage by alkaline comet assay in maintenance hemodialysis subjects with hepatitis C infection. Mutat Res 596:137–142CrossRefPubMedGoogle Scholar
  56. 56.
    Tice RR, Agurell E, Anderson D et al (2000) Single cell gel/Comet Assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221CrossRefGoogle Scholar
  57. 57.
    Collins AR (2004) The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26:249–261CrossRefPubMedGoogle Scholar
  58. 58.
    OECD (2001) Prenatal developmental toxicity study. In: Guideline for the testing of chemicals. https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecd_gl414.pdf. Accessed 14 May 2017
  59. 59.
    Okada A, Kurihara H, Aoki Y et al (2004) Amidic modification of valproic acid reduces skeletal teratogenicity in mice. Birth Defects Res (Part B) 71:47–53CrossRefGoogle Scholar
  60. 60.
    Canimoglu S (2009) Maltitol’un sicanlarda mutagenik ve teratojenik etkileri (the mutagenic and teratogenic effects of maltitol in rats). Cukurova University Institute of Natural and Applied Science, Department of Biology, Doctorate thesis (Supervisor Rencuzogullari E), p 83Google Scholar
  61. 61.
    Canimoglu S, Rencuzogullari E (2013) The genotoxic and teratogenic effects of maltitol in rats. Toxicol Ind Health 29:935–943CrossRefPubMedGoogle Scholar
  62. 62.
    Menegola E, Broccia LM, Giavini E (2001) Atlas of rat fetal skeleton double stained for bone and cartilage. Teratology 64:125–133CrossRefPubMedGoogle Scholar
  63. 63.
    Perry PE, Thompson EJ (1984) The methodology of sister chromatid exchanges. In: Kilbey BJ, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedures, 2nd edn. Elsevier Sci BV, Amsterdam, pp 495–529CrossRefGoogle Scholar
  64. 64.
    Evans HJ (1984) Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. In: Kilbey BJ, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedures, 2nd edn. Elsevier Sci BV, Amsterdam, pp 405–427CrossRefGoogle Scholar
  65. 65.
    OECD (1986) Genetic toxicology: in vitro sister chromatid exchange assay in mammalian cells. In: Guideline for the testing of chemicals. http://www.oecd-ilibrary.org/environment/test-no-479-genetic-toxicology-in-vitro-sister-chromatid-exchange-assay-in-mammalian-cells_9789264071384-en. Accessed 11 Mar 2017
  66. 66.
    OECD (1997) In vitro mammalian chromosome aberration. In: Guideline for the testing of chemicals. http://www.oecd.org/chemicalsafety/risk-assessment/1948434.pdf. Accessed 11 Mar 2017
  67. 67.
    Kirsch-Volders M, Elhajouji A, Cundari E, Van Hummelen P (1997) The in vitro micronucleus test: a multi-endpoint assay to detect simultaneously mitotic delay, apoptosis, chromosome breakage, chromosome loss and non-disjunction. Mutat Res 392:19–30CrossRefPubMedGoogle Scholar
  68. 68.
    Fenech M (2000) The in vitro micronucleus technique. Mutat Res 455:81–95CrossRefPubMedGoogle Scholar
  69. 69.
    Green MH, Lowe JE, Delaney CA, Green IC (1996) Comet assay to detect nitric oxide-dependent DNA damage in mammalian cells. Methods Enzymol 269:243–266CrossRefPubMedGoogle Scholar
  70. 70.
    McKelvey-Martin VJ, Green MH, Schmezer P et al (1993) The single cell gel electrophoresis assay (comet assay): a European review. Mutat Res 288:47–63CrossRefPubMedGoogle Scholar
  71. 71.
    Kopar N (2010) Salvia fruticosa bitki ekstraktinin metabolik aktivator varliginda ve yoklugunda insan lenfositlerinde genotoksik ve anti-genotoksik etkisi (the genotoxic and anti-genotoxic effects of Salvia fruticosa plant extract in human lymphocytes in the absence and presence of metabolic activator). Cukurova University, Institute of Natural and Applied Science, Department of Biology, Master thesis (Supervisor Rencuzogullari E), p 84Google Scholar
  72. 72.
    Hernández-Ceruelos A, Madrigal-Santillán E, Morales-González JA et al (2010) Antigenotoxic effect of Chamomilla recutita (L.) Rauschert essential oil in mouse spermatogonial cells, and determination of its antioxidant capacity in vitro. Int J Mol Sci 11:3793–3802CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biology, Faculty of Science and LettersAdiyaman UniversityAdiyamanTurkey

Personalised recommendations