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In Vitro Genotoxicity Assessment and the Effects of 4-Quinolones upon Human Cells

  • G. C. Crumplin
Part of the Springer Series in Applied Biology book series (SSAPPL.BIOLOGY)

Abstract

The last five years have seen the emergence of several new derivatives of Nalidixic acid which display great antibacterial potency and broad-spectrum antibacterial activity. Recent national and international meetings have clearly demonstrated that this group of compounds, known collectively as the 4-quinolones, are at present the most intensively studied group of antibacterial chemotherapeutic agents. Evidence is rapidly accumulating which suggests that these agents have the potential to become amongst the most exciting and challenging clinical agents to enter clinical use since the advent of the ß-lactams. The 4-quinolones act through a uniquely complex mechanism of action upon DNA topoisomerases. These enzymes control the spatial geometry of the cellular DNA and in molecular biology they are providing new insights into how cells perform the routine mechanical tasks of replicating DNA and transcribing the genetic information. It is becoming increasingly evident that the DNA topoisomerases are fundamentally important in sustaining the normal life-processes of all cellular organisms from the simple bacterium through to Homo sapiens.

Keywords

Anti Bacterial Agent Nalidixic Acid Sister Chromatid Exchange Genotoxic Potential Pipemidic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ames BN, McCann J and Yamasaki E (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test Mutat Res 31:347–364PubMedGoogle Scholar
  2. Ashby J, Styles JA and Paton D (1980) Studies in vitro to discern structural requirements for carcinogenicity in analogues of the carcinogen 4-dimethylaminoazobenzene (butter yellow). Carcinogenesis 1:1–7PubMedCrossRefGoogle Scholar
  3. Barrett JF, Gootz TD, McGuirck PR, Farrell C, Sokolowski S and Frescura M (1987) Use of in vitro topoisomerase II assays in studying nalidixic acid derivatives. XXV ICAAC (New York)Google Scholar
  4. Birkett DA, Garrett M and Stevenson CJ (1969) Phototoxic buUous eruptions due to Nalidixic acid. Brit J Dermatol 81:324–344CrossRefGoogle Scholar
  5. Bond CM (1988) Studies of DNA topoisomerases of human origin PhD Thesis University of York) Burry JN (1974) Persistent phototoxicity due to Nalidixic acid.Arch Dermatol 109:263Google Scholar
  6. Cairns J (1981) The origin of human cancers.Nature 289:353–357PubMedCrossRefGoogle Scholar
  7. Chao L (1978) An unusual interaction between the target of nalidixic acid and novobiocin. Nature 271:385–386PubMedCrossRefGoogle Scholar
  8. Chow K-C and Pearson GD (1985) Adenovirus infection elevates levels of cellular topoisomerase I Proc Nad Acad Sci 82:2247–2251CrossRefGoogle Scholar
  9. Clive D, Flamm WG, Machesko MR and Bernheim NJ (1972) A mutational assay system using the thymidine kinase locus in mouse lymphoma cells. Mutat Res 16:77–87PubMedCrossRefGoogle Scholar
  10. Clive D and Spector JFS (1975) Laboratory procedure for assessing specific locus mutations at the TK locus in cultured L5178Y mouse lymphoma cells. Mutat Res. 31 17–29PubMedGoogle Scholar
  11. Cook TM, Goss WA and Deitz WH (1966) Mechanism of action of Nalidixic acid on Escherichia coli V Possible mutagenic effect. J Bacteriol 91:780–783PubMedGoogle Scholar
  12. Crumplin GC(1981) The involvement of DNA topoisomerases in DNA repair and mutagenisis. Carcinogenisis 2:157–160CrossRefGoogle Scholar
  13. Crumplin GC (1985) The mechanisms of action of 4-quinolone antibacterials. ASM annual meeting (Las Vegas)Google Scholar
  14. Crumplin GC and Smith JT (1975) Nalidixic acid: an antibacterial paradox Antimicrob. Ag. Chemother 8:251–261Google Scholar
  15. Crumplin GC and Smith JT (1981) The effect of R factors on host cell responses to Nalidixic acid: I Increased susceptibility of Nalidixic acid sensitive hosts. Antimicrob Chemother 7:379–388CrossRefGoogle Scholar
  16. Czinn S J, Speck WT and Rosenkranz HS (1981) Abnormalities in the development of the American sea urchin induced by Nalidixic acid. Mutat Res.91:l19–121CrossRefGoogle Scholar
  17. Degnen GE (1974) A conditional mutator gene, MutD, in Escherichia coli. PhD Thesis Princeton UniversityGoogle Scholar
  18. De Marini DM, Brock KL, Doerr CL and Moore MM (1986) Mutagenicity of topoisomerase II active drugs due to clastogenic mechanisms.First Conference on DNA topoisomerases in cancer chemotherapy (New York Nov 19–20)Google Scholar
  19. Domagala JM, Hanna LD, Heifitz CL, Hutt MP, Mich TF and Solomon P (1986) New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay. J Med Chem 29:394–404PubMedCrossRefGoogle Scholar
  20. Eamshaw WC and Heck MMS (1985) Localization of topoisomerase E in mitotic chromosomes. J Cell Biology 100:1716–1725CrossRefGoogle Scholar
  21. Earnshaw WC, Halligan B, Cooke CA, Heck MMS and Liu LF (1985) Topoisomerase II is a structural component of mitotic chromosome scaffolds. J Cell Biology 100:1706–1715CrossRefGoogle Scholar
  22. Easmon CSF and Crane JP (1985) Uptake of ciprofloxacin by macrophages. J Clin Pathol 38:442–444PubMedCrossRefGoogle Scholar
  23. Easmon CSF and Crane J (1986) Uptake of Ro 23–6420 by phagocytic cells XXVIth ICAAC (New Orleans) abstr 947Google Scholar
  24. Echols H (1981) SOS functions, cancer and inducible evolution. Cell 25:1–2PubMedCrossRefGoogle Scholar
  25. Firkin FC and Clark-Walker GD (1979) Abnormal mitochondrial DNA in acute leukaemia and lymphoma, Brit J Haematol 43:201–206CrossRefGoogle Scholar
  26. Furth EE, Thmy WG, Penman BW, Liber HL and R and WM (1981) Quantitative assay for mutation in diploid human lymphoblasts using microtitre plates. Analyt Biochem 110:1–8PubMedCrossRefGoogle Scholar
  27. Garner RC (1980) In vitro assays to predict carcinogenicity? In Short-term test systems for detecting carcinogens, (eds. KH Norpoth and RC Gamer) pub. Springer-Verlag pp 5–18CrossRefGoogle Scholar
  28. German A, Panouse-Perrin J and Ardouin AC (1969) Mutagenic action of Nalidixic acid on Staphylococcus phage.CR Acad Sci Paris 268:1827–1829Google Scholar
  29. Green MHL and Muriel WJ (1976) Mutagen testing using trp + reversion in Escherichia coli Mutat Res 38:3–32Google Scholar
  30. Green MHL and Muriel WJ (1976) Mutagen testing using trp + reversion in Escherichia coli Mutat Res 38:3–32PubMedGoogle Scholar
  31. Hartley HO and Sielken RL (1977) Estimation of “Safe Doses” in carcinogenic experiments. Biometrics 33:1–30PubMedCrossRefGoogle Scholar
  32. Holden HE, Barrett JF, Huntington CM, Muehlbauer PA and Wahrenburg MG (1989) Genetic profile of a naidixic acid analog: A model for the mechanism of sister chromatid exchange induction.Environmental Mutagenesis 13:(in press)Google Scholar
  33. Hosomi J and Irikura T (1981) The mutagenicity of AM-715 in vitro.Chemotherapy 29 (S-4):938–945Google Scholar
  34. Hosomi J, Maeda A, Oomori Y, Irikura T and Yokota T (1988) Mutagenicity of norfloxacin and AM-833 in bacteria and mammalian cells Rev Infect Dis. 10 (suppl. 1):S148Google Scholar
  35. Bceda S, Yazawa M and Nishimura C (1987) Antiviral activity and inhibition of topoisomerase by Ofloxacin, a new quinolone derivative. Antiviral Research 8:103–113CrossRefGoogle Scholar
  36. Irikura T, Suzuki H and Sugimoto T (1981) Mutagenicity studies of AM-715 in animals Chemotherapy 29 (S-4);932–937Google Scholar
  37. Itoh T and Tomizawa J-I (1977) Involvement of DNA gyrase in bacteriophage T7 DNA replication.Nature 270:78–80PubMedCrossRefGoogle Scholar
  38. Kada T and Hirano K (1980) Screening of environmental chemical mutagens by the rec assay system with Bacillus subtil is.in Chemical mutagens Principles and methods for their detection vol.6, (ed FJ de Serres) pub Plenum Press: 149–173Google Scholar
  39. Kanisawa M, Katoh H and Aiso K (1974) Carcinogenicity of potassium l-methyl-7-[2-(5-nitro-2-furyl)-vinyl] -4-oxo-l,4-dihydro-l,8-naphthyridine-3-carboxylate in ICR mice.Gann 65:1–11PubMedGoogle Scholar
  40. Kohn KW (1979) DNA as a target in cancer chemotherapy: Measurement of macromolecular DNA damage produced in mammalian cells by anticancer agents and carcinogens.In Methods in Cancer Research Vol. XVL (Academic Press):291–345Google Scholar
  41. Kowalczyk J (1980) Sister chromatid exchanges in children treated with Nalidixic acid. Mutat Res 77:371–375PubMedCrossRefGoogle Scholar
  42. Kreuzer KN, McEntee K, Geballe AP and Cozzarelli NR (1978) Lambda-transducing phages for the nalA gene of E. coli and conditional lethal mutations. Molec Gen Genet:167:129–137PubMedCrossRefGoogle Scholar
  43. Latt SA and Schreck RR (1980) Sister chromatid exchange analysis. Amer J Hum Genet 32:297–313PubMedGoogle Scholar
  44. Lode H, Hoffken G, Prinzing C, Glatzel P, Wiley R, Olschewski P, Sievers B, Reimnitz D, Borner K and Koeppe P (1987) Comparative pharmacokinetics of new 4-quinolones. Drugs 34:(Suppl.l) 21–25PubMedCrossRefGoogle Scholar
  45. Louis P, Wiskemann A and Schulz KH (1973) Bullous Photodermatitis following Nalidixic acid. Hautaitz 24:445–448Google Scholar
  46. Marians KJ, Bceda J-E, Schlagman S. and Hurwitz J (1978) Role of DNA gyrase in FX replicative form replication in vitro Proc Natl Acad Sci 74: 1965–1968CrossRefGoogle Scholar
  47. Martin CN, McDermid AC and Garner RC (1977) Measurement of unscheduled DNA synthesis in HeLa cells by liquid scintillation counting after carcinogen treatment.Cancer Letters 2:355–360PubMedCrossRefGoogle Scholar
  48. Martin CN, McDermid AC and Gamer RC (1978) Testing of known carcinogens and non-carcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells. Cancer Res 38:2621–2627PubMedGoogle Scholar
  49. Mattem MR and Scudiero DA (1981) Dependence of mammalian DNA synthesis on DNA supercoüing. IQ Characterization of the inhibition of replicative and repair-type DNA synthesis by novobiocin and Nalidixic acid. Biochim Biophys Acta 653: 248–258Google Scholar
  50. Maura A and Pino A (1988) Evaluation of the DNA-damaging and mutagenic activity of oxolinic and Pipemidic acids by the granuloma pouch assay. Mutagenisis (in press)Google Scholar
  51. Mayer D and Bruch K (1985) Kein hin weis fur mutagenitat von ofloxacin. Infection (in press)Google Scholar
  52. McChesney EW, Froelich EJ, Lesher GY,Crain AVR and Rosi D (1964) Absorption, excretion and metabolism of a new antibacterial agent, Nalidixic acid.Toxicol. App Pharmacol 6:292–309CrossRefGoogle Scholar
  53. McCoy EC, Petnülo LA and Rosenkranz HS (1980) Non-mutagenic genotoxicants: Novobiocin and Nalidixic acid, two inhibitors of DNA gyrase. Mutat Res 79:33–43PubMedCrossRefGoogle Scholar
  54. McDaniel LS, Rogers LH and Hill WE (1980) Survival of recombination deficient mutants of Escherichia coli during incubation with Nalidixic acid. J Bacteriol 134:1195–1198Google Scholar
  55. McQueen CA. and Williams GA (1987) Effects of quinolone antibiotics in tests for genotoxicity.Amer J Med 82, Suppl 4A:94–96Google Scholar
  56. Melcion C and Cordier A (1986) Absence of genotoxicity of quinolones to mammalian cells.Intemational Symp New Quinolones (Geneva)Google Scholar
  57. Miltenberger HC (1985) cited in: Ofloxacin: Keine Anhaltspunkte fur mutagene Wirkungen.Arztliche Praxis 37:3482Google Scholar
  58. Mirkin SM, Zaitsev EN, Panyutin IG and Lyamichev VI (1984) Native supercoüing of DNA: The effects of DNA gyrase and ω protein in E. coli Molec Gen Genet 196:508–512PubMedCrossRefGoogle Scholar
  59. Mizuuchi K, Geliert M and Nash HA (1978) Involvement of supertwisted DNA in integrative recombination of bacteriophage lambda J Molec Biol 121:375–392PubMedCrossRefGoogle Scholar
  60. Moreau P and Devoret R (1977) Potential carcinogens tested by induction and mutagens of prophage λ In Escherichia coli K12.In Origins of human cancer book C (eds HH Hiatt and JD Watson) Pub Cold Spring Harbor Labs: 1451–1472Google Scholar
  61. Morita J, Watanabe K and Komano T (1984) Mechanism of action of new synthetic nalidixic acid-related antibiotics: Inhibition of DNA supercoiling catalyzed by DNA gyrase.Agric Biol Chem 48:663–668CrossRefGoogle Scholar
  62. Phillips I, Culebras E, Moreno F and Baquero F (1987) Induction of SOS response by 4-quinolones.J Antimicrob Chemother 20:631–638PubMedCrossRefGoogle Scholar
  63. Priel E, Aboud M, Feifelman H and Segal S (1985) Topoisomerase II activity in human leukemic and lymphoblastoid cells. Biochem Biophys Res. Comm 130:325–332PubMedCrossRefGoogle Scholar
  64. Ramsay CA and Obreshkova E (1974) Photosensitivity from Nalidixic acid. Br J Dermatol 91:523–528PubMedCrossRefGoogle Scholar
  65. Ratcliffe NR (1985) Bacterial responses to antigyral agents. PhD Thesis University of LondonGoogle Scholar
  66. Ratcliffe NR and Smith JT (1984) The mechanism of reduced activity of 4-quinolone agents in urine. FAC:563–569Google Scholar
  67. Rosenkranz HS and Lambek C (1965) In vivo effects of nalidixic acid on the DNA of human diploid cells in tissue culture. Proc Soc Exp Biol Med 120:549–552PubMedGoogle Scholar
  68. Rosenkranz HS and Leifer Z (1980) Detection of carcinogens and mutagens with repair-deficient bacteria. In Chemical mutagens — Principles and methods for their detection vol.6 (ed FJ.de Serres) Plenum press:109–147Google Scholar
  69. Saito A, Sawatari K, Fukuda Y, Nagasawa M, Koga H, Tomonaga A, Nakazato H, Fujita K, Shigeno Y, Suzuyama Y, Yamguchi K, Izumikawa K and Hara K (1985) Susceptibility of Legionella pneumophila to Ofloxacin in vitro and in experimental Legionella pneumonia in guinea pigs.Antimicrob Ag Chemother 28:15–20Google Scholar
  70. Sanzey B (1979) Modulation of gene-expression by drugs affecting DNA gyrase. J Bacteriol 138:40–47PubMedGoogle Scholar
  71. Schlüter G (1986) Toxicology of Ciprofloxacin, Proc. First Int. Ciprofloxacin Workshop (eds HC Neu and H Weuta) pp 61–67 (pub. Exerpta Medica, Amsterdam)Google Scholar
  72. Shen LL and Pernet AG (1985) Mechanism of inhibiton of DNA gyrase by analogues of Nalidixic acid: The target of the drug is DNA. Proc Natl Acad Sci 82:307–311PubMedCrossRefGoogle Scholar
  73. Shimada H, Morita H and Akimoto T (1980) Lack of induction of dominant lethal mutations in male mice by Nalidixic acid. Mutat Res 7:165–170Google Scholar
  74. Shimada H, Ebine Y, Kurosawa Y and Aranchi T (1984) Mutagenicity studies of DL-8280, a new antibacterial drug.Chemotherapy 32:1162–1170Google Scholar
  75. Shimada H, Ebine Y, Kurosawa Y and Aranchi T (1985) Dominant lethal study in male mice treated with ofloxacin, a new antibacterial drug. Mutat Res 114:51–55CrossRefGoogle Scholar
  76. Smith CL, Kubo M and Imamato F (1978) Promoter specific inhibition of transcription by antibiotics which act on DNA gyrase. Nature 275:420–423PubMedCrossRefGoogle Scholar
  77. Smith JT (1984) Awakening the slumbering potential of the 4-quinolone antibacterials. Pharm J 233:299–305Google Scholar
  78. Stenchever MA, Powell W and Jarvis JA (1970) Effects of Nalidixic acid on human chromosome integrity. Amer J Obstet Gynaec 107:329–330Google Scholar
  79. Stevens PJE (1980) Bactericidal effect against E. coli of Nalidixic acid and four structurally related compounds. J Antimicrob Chemother 6:535–542PubMedCrossRefGoogle Scholar
  80. Styles JA (1977) A method for detecting carcinogenic organic chemicals using mammalian cells in culture. Brit J Cancer 36:558–563PubMedCrossRefGoogle Scholar
  81. Tokunaga Y, Asaba M and Kato R (1979) Dominant lethal mutation test of Miloxacin, a new synthetic antibacterial agent. Pharmacometrics 18:37–45Google Scholar
  82. Vigier PRR (1974) Effet mutagene de l’acide nalidixique sur le bacteriophage T4.Mutat Res 25:25–32PubMedCrossRefGoogle Scholar
  83. Winshell EB and Rosenkranz HS (1970) Nalidixic acid and the metabolism of Escherichia coli J Bacteriol 104:1168–1175PubMedGoogle Scholar
  84. Witkin EM and Wermundsen IE (1979) Targeted and untargetedmutagenesis by various inducers of SOS functions in Escherichia coli Cold Spring Harbor Symp Quant Biol 43:881–886PubMedCrossRefGoogle Scholar
  85. Zelickson AS (1964) Phototoxic reactions with Nalidixic acid. J Amer Med Ass 190:556–557CrossRefGoogle Scholar

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© Springer-Verlag London Limited 1990

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  • G. C. Crumplin

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