Adaptability of Microbial Mutagenicity Assays to the Study of Problem of Environmental Concern

  • Herbert S. Rosenkranz
  • George E. Karpinsky
  • Monika Anders
  • George DeMarco
  • E. Joshua Rosenkranz
  • Lynn A. Petrullo
  • Elena C. McCoy
  • Robert Mermelstein
Part of the Basic Life Sciences book series (volume 15)


It is now well recognized that short-term microbial assays, when run under carefully controlled conditions, have predictive value for the detection of the potential cancer-causing properties of most classes of chemicals. Indeed, our Laboratory has participated both in the development and validation of such assays. However, in an eagerness to obtain reliable data relating to the potential genotoxic and/or carcinogenic potentials, too much emphasis has been placed on procedural details such that sight is lost of the fact that these assays lend themselves — when suitably modified — to the elucidation of some basic biological problems. There is an increasing number of these which can be used to illustrate this point. The present report, however, deals primarily with data obtained in our own Laboratories.


Polycyclic Aromatic Hydrocarbon Bile Acid Anaerobic Bacterium Colon Carcinogenesis Zinc Dust 
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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  1. 1.
    B.N. Ames, J. McCann, and E. Yamasaki, Methods for detecting carcinogens and mutagens with the Salmonella/microsome mutagenicity test. Mutation Res. 31: 347 (1975).PubMedGoogle Scholar
  2. 2.
    B.S. Reddy, J.H. Weisburger, T. Narisawa, and E.L. Wynder Colon carcinogenesis in germ-free rats with 1,2-Dimethylhydrazine and N-Methyl-N’-nitro-N-nitrosoguanidine, Cancer Res. 34: 2368, (1974).PubMedGoogle Scholar
  3. 3.
    B.S. Reddy, T. Narisawa, P. Wright, D. Vukushich, J.H. Weisburger, and E.L. Wynder, Colon carcinogenesis with azoxymethane and dimethylhydrazine in germ-free rats, Cancer Res. 35: 287 (1975).PubMedGoogle Scholar
  4. 4.
    M.J. Hill, Bacteria and the etiology of colon cancer, Cancer 34: 815 (1974).PubMedCrossRefGoogle Scholar
  5. 5.
    M.J. Hill, Metabolic epidemiology of dietary factors in large bowel cancer, Cancer Res. 35: 3398 (1975).PubMedGoogle Scholar
  6. 6.
    M.J. Hill, Role of colon anaerobes in the metabolism of bile acids and steroids, and its relation to colon cancer, Cancer 36: 2387 (1975).PubMedCrossRefGoogle Scholar
  7. 7.
    M.H. Hill, The role of unsaturated bile acids in the etiology of large bowel cancer, in: “Origins of human cancer, Book C,” H.H. Hiatt, J.D. Watson, and J.A. Winstein, eds., Cold Spring Harbor Laboratory, (1977).Google Scholar
  8. 8.
    W.E.C. Moore and L.V. Holdeman, Discussion of current bacteriological investigations of the relationship between intestinal flora, diet and colon cancer, Cancer Res. 35: 3418 (1975).Google Scholar
  9. 9.
    S.M. Finegold, V.L. Sutter, P.T. Sugihara, H.A. Elder, S.M. Lehmann. and R.L. Phillips, Fecal microbial flora in Seventh-day Adventist population and control subiects, Am. J. Clin. Nutr, 30: 1781 (1977).PubMedGoogle Scholar
  10. 10.
    J. Slemrova and R. Edenharden, Die Bedeutung des bakteriellen Steroidabbau für die Atiologie des Dickdarmkrebses. VII. Zur Methodik der Identifizierung von Gallensäureabbauprodukten, Zentralbl. Bakteriol. (Orig. B) 164: 236 (1977).Google Scholar
  11. 11.
    B. Goldin and S.L. Gorbach, Alteration in fecal microflora enzymes related to diet, age, Lactobacillus supplements and dimethylhydrazine, Cancer 40: 2421.Google Scholar
  12. 12.
    E.L. Wynder, Nutrition and cancer, Fed. Proc. 36: 1309 (1976).Google Scholar
  13. B.S. Reddy, T. Narisawa, R. Maronpot, J.H. Weisburger and E.L. Wynder, Animal models for the study of dietary factors and cancer of the large bowel, Cancer Res. 35: 3421 (1975).PubMedGoogle Scholar
  14. 14.
    B.S. Reddy, A. Mastromarino and E.L. Wynder, Further leads on metabolic epidemiology of large bowel cancer, Cancer Res. 35: 3403 (1975).PubMedGoogle Scholar
  15. 15.
    B.S. Reddy, J.H. Weisburger and E.L. Wynder, Effect of high and low risk diets for colon carcinogenesis on fecal microflora and steroids in man, J. Nutr. 105: 878 (1975).PubMedGoogle Scholar
  16. 16.
    B.S. Reddy, S. Mangat, A. Sheinfil, J.H. Weisburger and E.L. Wynder, Effect of type and amount of diety fat and 1,2-dimethylhydrazine on biliary bile acids, fecal bile acids, and neutral sterols in rats, Cancer Res. 37: 2132 (1977).PubMedGoogle Scholar
  17. 17.
    A.B. Lowenfels and M.E. Anderson, Diet and cancer, Cancer 39: 1809 (1977).PubMedCrossRefGoogle Scholar
  18. 18.
    R.S. Klein, M.T. Catalano, S.C. Edberg, J.I. Casey, and N.H. Steigbigel, Streptococcus bovis septicemia and carcinoma of the colon, Annals Intern. Med. 91: 560 (1979).Google Scholar
  19. 19.
    H.S. Rosenkranz and W.T. Speck, Mutagenicity of metronidazole: activation by mammalian liver microsomes, Biochem. Biophys. Res. Commun. 66: 520 (1975).CrossRefGoogle Scholar
  20. 20.
    R. Mermelstein, E. McCoy and H.S. Rosenkranz, The microbial mutagenicity of nitroarenes, in: “The genotoxic effects of airborne agents,” Brookhaven National Laboratory Symposium, in press.Google Scholar
  21. 21.
    H.S. Rosenkranz and R. Mermelstein, The Salmonella mutagenicity and the E. coli Pol A+/Pol Al- Repair assays: Evaluation of relevance to carcinogenesis, in: “The Predictive Value of Short-Term Screening Tests in the Evaluation of Carcinogenicity,” G.M. Williams, R. Kores, H.W. Waaijers, and K.W. van de Poll, eds., Elsevier/North Holland (1980).Google Scholar
  22. 22.
    G.E. Karpinsky, E.C. McCoy, H.S. Rosenkranz and R. Mermelstein, The chemical activation of non-mutagenic nitrated poly-cyclic aromatic hydrocarbons to mutagens, Mut. Res. (1982).Google Scholar
  23. 23.
    R.B. Haveland-Smith and R.D. Combes, Genotoxicity of the food colours Red 2G and Brown FK in bacterial systems; use of structurally-related dyes and azo-reduction, Fd. Cosmet. Toxicol. 18: 223 (1980).CrossRefGoogle Scholar
  24. 24.
    J.P. Brown and P.S. Dietrich, Mutagenicity of anthraquinone and benzanthrone derivatives in the Salmonella/microsome test: Activation of anthraquinone glycosides by enzymic extracts of rat cecal bacteria, Mutation Res. 66: 9 (1979).PubMedCrossRefGoogle Scholar
  25. 25.
    J.P. Brown, A review of the genetic effects of naturally occurring flavonoids, anthraquinones and related compounds, Mutation Res. 75: 243 (1980).PubMedGoogle Scholar
  26. 26.
    C.P. Hartman, G.E. Fulk and A.W. Andrews, Azo reduction of trypan blue to a known carcinogen by a cell-free extract of a human intestinal anaerobe, Mutation Res. 58: 125 (1978).PubMedCrossRefGoogle Scholar
  27. 27.
    T. Narisawa, N.E. Magadia, J.H. Weisburger, and E.L. Wynder, Promoting effect of bile acids on colon carcinogenesis after intrarectal instillation of N-methyl-N’-nitro-Nnitrosoquanidine in rats. J. Natl. Cancer Inst. 55: 1093 (1974).Google Scholar
  28. 28.
    B.S. Reddy, Role of bile metabolites in colon carcinogenesis. Cancer 36: 2401 (1975).PubMedCrossRefGoogle Scholar
  29. 29.
    B,S. Reddy, T. Narasawa, J.H. Weisburger, and E.L. Wynder, Promoting effect of sodium deoxycholate on colon adenocarcinoma in germfree rats, J. Natl. Cancer Inst. 56: 441 (1976).Google Scholar
  30. 30.
    A.B. Lowenfels, Does bile promote extra-colonic cancer? Lancet 7: 239 (1978).CrossRefGoogle Scholar
  31. 31.
    B.S. Reddy, K. Watanabe, J.H. Weisburger and E.L. Wynder, Promoting effect of bile acids in colon carcinogenesis in germ-free and conventional F33 rats, Cancer Res. 37: 3238 (1977).PubMedGoogle Scholar
  32. 32.
    S.J. Silverman and A.W. Andrews, Bile acids, co-mutagenic activity in the Salmonella-mammalian microsome mutagenicity test, J. Natl. Cancer Inst. 59: 1557 (1977).PubMedGoogle Scholar
  33. 33.
    B.S. Reddy and K. Watanabe, Effect of cholesterol metabolites and promoting effect of lithocholic acid in colon carcinogenesis in germ-free and conventional F344 rats, Cancer Res. 39: 1521 (1979).PubMedGoogle Scholar
  34. 34.
    H.S. Rosenkranz, E.C. McCoy, D.R. Sanders, M. Butler, D.K. Kiriazides and R. Mermelstein, Nitropyrenes: isolation, identification and reduction of mutagenic impurities in a carbon black and toners, Science 209: 1039 (1980).PubMedCrossRefGoogle Scholar
  35. 35.
    H.S. Rosenkranz and W.T. Speck, Activation of nitrofurantoin to a mutagen by rat liver nitroreductase, Biochem. Pharmacol. 25: 1555 (1976).Google Scholar
  36. 36.
    H.S. Rosenkranz and L.A. Poirier, An evaluation of the mutagenicity and DNA modifying activity in microbial systems of carcinogens and non-carcinogens, J. Natl. Cancer Inst. 62: 873 (1979).PubMedGoogle Scholar
  37. 37.
    J.L. Blumer, A. Friedman, L.W. Meyer, E. Fairchild, L.T. Webster, Jr. and W.T. Speck, Relative importance of bacterial and mammalian nitroreductases for niridazole mutagenesis, Cancer Res. in press (1981).Google Scholar
  38. 38.
    W.T. Speck and H.S. Rosenkranz, Base substitution mutations induced in Salmonella strains by visible light (450 nm), Photochem. Photobiol. 21: 369 (1975).CrossRefGoogle Scholar
  39. 39.
    W.T. Speck and H.S. Rosenkranz, Phototherapy for neonatal hyperbilirubinemia - A potential environmental health hazard to newborn infants: A review, Environm. Mutagenesis 1: 321 (1979).CrossRefGoogle Scholar
  40. 40.
    E.C. McCoy, J. Hyman and H.S. Rosenkranz, Conversion of environmental pollutants to mutagens by visible light, Biochem. Biophys. Res. Comm. 89: 729 (1979).CrossRefGoogle Scholar
  41. 41.
    G. Löfroth, E. Hefner, I. Alfheim and M. Moller, Mutagenic activity in photocopies, Science 209: 1037 (1980).PubMedCrossRefGoogle Scholar
  42. 42.
    T.C. Pederson and J.-S. Siak, The role of nitroaromatic compounds in the direct-acting mutagenicity of Diesel particle extracts, J. Appl. Toxicol. in press.Google Scholar
  43. 43.
    D. Schuetzle, F.S.-C. Lee, T.J. Prater and S.B. Tejada, The identification of polynuclear aromatic hydrocarbon derivatives in mutagenic fractions of Diesel particulate extracts, Intern. J. Environm. Analyt. Chem. 9: 1 (1981).CrossRefGoogle Scholar
  44. 44.
    G. Lgfroth, Comparison of the mutagenic activity from Diesel and gasoline powered motor vehicles to carbon particulate matter, in: “Second symposium on application of complex environmental mixtures,” Plenum Press, in press (1981).Google Scholar
  45. 45.
    T.C. Pederson and J. Sisk, Characterization of direct-acting mutagens in Diesel exhaust particulates by thin-layer chromatography, Ann. Meeting Amer. Chem. Soc. Abstracts, Div. Environm. Chem. (1980).Google Scholar
  46. 46.
    D. Schuetzle, T.J. Prater, T. Riley, A. Durisin and I. Salmeen, Analysis of nitrated derivatives of PAH and determination of their contribution to Ames assay mutagenicity for Diesel particulate extracts, Fifth Intern. Symp. Polynuclear Aromatic Hydrocarbons, Columbus, Ohio Abstracts.Google Scholar
  47. 47.
    J.N. Pitts, Jr., K.A. Van Cauwenberghe, D. Grosjean, J.P. Schmid, D.R. Fitz, W.L. Belser, Jr., G.B. Knudson and P.M. Hynds, Atmospheric reactions of polycyclic aromatic hydrocarbons: Facile formation of mutagenic nitro derivatives, Science 202: 515 (1978).Google Scholar
  48. 48.
    J.N. Pitts, Jr., Photochemical and biological implications of the atmospheric reactions of amines and benzo(a) pyrene, Phil. Trans. Royal Soc. London A, 290: 551 (1979).Google Scholar
  49. 49.
    J. Jager, Detection and characterization of nitro derivatives of some polycyclic aromatic hydrocarbons by fluorescence quenching after thin-layer chromatography: Application to air pollution analysis, J. Chromatog. 152: 575 (1978).CrossRefGoogle Scholar
  50. 50.
    Y.Y. Wang, S.M. Rappaport, R.F. Sawyer, R.E. Talcott and E.T. Wei, Direct-acting mutagens in automobile exhaust, Cancer Letters 5: 39 (1979).CrossRefGoogle Scholar
  51. 51.
    H. Tokiwa, R. Nakagawa, K. Morita and Kamachi, Analysis of mutagenic nitro compounds in environmental samples (in Japanese), Environmental Mutagen Soc. of Japan, Abstracts, p. 18 (1979).Google Scholar
  52. 52.
    C.M. King, C.Y. Wang and P.O. Warner, Evidence for the presence of nitro aromatics in airborne particulates, Proc. Amer. Assoc. Cancer. 1es. p. 83 (1980).Google Scholar
  53. 53.
    H.E. Kubitscheck, and D.M. Williams, Mutagenicity of fly ash from fluidized - bed combuster during start-up and steady state operating conditions, Mutation Res. 77: 287 (1980).CrossRefGoogle Scholar
  54. 54.
    E.T. Wei, Y.Y. Wang and S.M. Rappaport, Diesel emissions and the Ames test: A commentary, J. Air Poll. Control. Assoc. 30: 267 (1980).CrossRefGoogle Scholar
  55. 55.
    C.Y. Wang, M.S. Lee, C.M. King and P.O. Warner, Evidence for nitroaromatics as directing-acting mutagens of airborne-particulates, Chemosphere 9: 83 (1980).CrossRefGoogle Scholar
  56. 56.
    National Academy of Sciences, U.S., Health Effects of Exposure to Diesel Exhaust. The Report of the Health Effects Panel of the Diesel Impact Study Committee, National Research Council - National Academy of Sciences, Washington, D.C.Google Scholar
  57. 57.
    H. Tokiwa, R. Nakagawa, K. Morita, and Y. Ohnishi, Mutagenicity of nitro-derivatives induced by exposure of aromatic compounds to nitrogen dioxide, Mutation Res. in press.Google Scholar
  58. 58.
    J.N. Pitts, Jr., A.M. Winer, D.M. Lokensgard, S.D. Shaffer, E.C. Tuazon and G.W. Harris, Interactions between diesel emissions and gaseous co-pollutants in photochemical air pollution: Some health implications, Proc. EPA Intern. Symp. “Health Effects of Diesel Engine Emissions”, in press.Google Scholar
  59. 59.
    Anonymous, New burner reduces nitrogen oxide emissions, Chem. Eng. News. March 30, p. 19 (1981).Google Scholar
  60. 60.
    R.L. Bradow, Diesel particle emissions, Bull. N.Y. Acad. Med. 56: 797 (1980).PubMedGoogle Scholar
  61. 61.
    R. Mermelstein, D.K. Kiriazides, M. Butler, E.C. McCoy, and H.S. Rosenkranz, The extraordinary mutagenicity of nitropyrenes in bacteria, Mutation Res. in press.Google Scholar
  62. 62.
    W.T. Speck, S.L. Blumer, E.J. Rosenkranz, and H.S. Rosenkranz, Nirizadole nitroreductase deficiency in bacteria: An effect of genotype on mutagenicity of niridazole, Cancer Res. in press (1981).Google Scholar
  63. 63.
    V.W. Mayer, and C.J. Goin, Induction of mitotic recombination by certain hair-dye chemicals in Saccharomyces cereyisiae, Mutation Res. 78: 243 (1980).PubMedCrossRefGoogle Scholar
  64. 64.
    C.F. Arle.t.t, J. Cole, B.C. Broughton, J. Lowe, and B,A. Bridges, Mutagenic effects in human and mouse cells by a nitropyrene in The Genotoxic Effects of Airborne Agents, Brookhaven Laboratory Symposium in press (1981)Google Scholar
  65. 65.
    E.C. McCoy, L.A. Petrullo, H,S. Rosenkranz, and R. Mermelstein 4-Nitroquinoline-l-oxide: Factors determining its mutagenicity in bacteria, Mutation Res. in press (1981).Google Scholar
  66. 66.
    P. Sims, Qualitative and quantitative studies on the metabolism of a series of aromatic hydrocarbons by rat-liver preparations, Biochem. Pharmacol. 19: 795 (1970).Google Scholar
  67. 67.
    E.C. McCoy, E.J. Rosenkranz, L.A. Petrullo, H.S. Rosenkranz and R. Merrmelstein, Structural basis of the mutagenicity in bacteria of nitrated naphthalene and derivatives, Environm. Mut. 3: in press (1981).Google Scholar
  68. 68.
    F.F. Kadlubar, J.A. Miller, and E.C. Miller, Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis, Cancer Res. 37: 805 (1977).PubMedGoogle Scholar
  69. 69.
    F.F. Kadlubar, J.J. Miller, and E.C. Miller, Guanyl 06- arylamidation and 06-arylation of DNA by the carcinogen N-hydroxyl-l-naphthylamine, Cancer Res. 38: 3628 (1978).PubMedGoogle Scholar
  70. 70.
    F.F. Kadlubar, L.E. Unruch, F.A. B.eland, K.M. Straub, and F.E. Evans, In vitro reaction of the carcinogen, N-hydroxy-2-naphthylamine, with DNA at the C-8 and N2 atoms of guanosine and at the N6 atom of adenine, Carcinogenesis 1:139 (1980).Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Herbert S. Rosenkranz
    • 1
  • George E. Karpinsky
    • 1
  • Monika Anders
    • 1
  • George DeMarco
    • 1
  • E. Joshua Rosenkranz
    • 1
  • Lynn A. Petrullo
    • 1
  • Elena C. McCoy
    • 1
  • Robert Mermelstein
    • 2
  1. 1.Department of MicrobiologyNew York Medical CollegeValhallaUSA
  2. 2.Joseph C. Wilson Center for TechnologyXerox CorporationRochesterUSA

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