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. 1985 Sep;50(3):649–655. doi: 10.1128/aem.50.3.649-655.1985

Fungal metabolism and detoxification of the nitropolycyclic aromatic hydrocarbon 1-nitropyrene.

C E Cerniglia, J P Freeman, G L White, R H Heflich, D W Miller
PMCID: PMC238683  PMID: 3907498

Abstract

Nitropolycyclic aromatic hydrocarbons are ubiquitous environmental pollutants, many of which are potent mutagens in bacterial and mammalian cells and carcinogenic to rodents. In this study, we investigated the fungal metabolism of 1-nitropyrene and determined the mutagenic activity of the metabolites toward Salmonella typhimurium TA98, TA98NR, and TA100. Cunninghamella elegans metabolized 1-nitropyrene to form glucoside conjugates of 6-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene. The metabolites were isolated by reversed-phase high-pressure liquid chromatography and characterized by application of UV absorption, 1H-nuclear magnetic resonance, and mass spectroscopy. Mutagenicity assays performed on samples extracted from incubations of C. elegans with 1-nitropyrene indicated that mutagenic activity decreased with time. Consistent with the loss in mutagenic activity, the glucoside conjugates of 6- and 8-hydroxy-1-nitropyrene were nonmutagenic in the Salmonella reversion assay. The results indicate that the fungus C. elegans metabolizes 1-nitropyrene to detoxified products.

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Selected References

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  1. Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
  2. Ball L. M., Kohan M. J., Claxton L. D., Lewtas J. Mutagenicity of derivatives and metabolites of 1-nitropyrene: activation by rat liver S9 and bacterial enzymes. Mutat Res. 1984 Nov-Dec;138(2-3):113–125. doi: 10.1016/0165-1218(84)90033-8. [DOI] [PubMed] [Google Scholar]
  3. Bond J. A., Medinsky M. A., Dutcher J. S. Metabolism of 1-[14C]nitropyrene in isolated perfused rat livers. Toxicol Appl Pharmacol. 1984 Sep 30;75(3):531–538. doi: 10.1016/0041-008x(84)90189-3. [DOI] [PubMed] [Google Scholar]
  4. Bryant D. W., McCalla D. R., Lultschik P., Quilliam M. A., McCarry B. E. Metabolism of 1,8-dinitropyrene by Salmonella typhimurium. Chem Biol Interact. 1984 May;49(3):351–368. doi: 10.1016/0009-2797(84)90108-x. [DOI] [PubMed] [Google Scholar]
  5. Cerniglia C. E., Howard P. C., Fu P. P., Franklin W. Metabolism of nitropolycyclic aromatic hydrocarbons by human intestinal microflora. Biochem Biophys Res Commun. 1984 Aug 30;123(1):262–270. doi: 10.1016/0006-291x(84)90407-8. [DOI] [PubMed] [Google Scholar]
  6. Cerniglia C. E., Miller D. W., Yang S. K., Freeman J. P. Effects of a fluoro substituent on the fungal metabolism of 1-fluoronaphthalene. Appl Environ Microbiol. 1984 Aug;48(2):294–300. doi: 10.1128/aem.48.2.294-300.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DiPaolo J. A., DeMarinis A. J., Chow F. L., Garner R. C., Martin C. N., Doniger J. Nitration of carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons results in products able to induce transformation of Syrian hamster cells. Carcinogenesis. 1983;4(3):357–359. doi: 10.1093/carcin/4.3.357. [DOI] [PubMed] [Google Scholar]
  8. El-Bayoumy K., Hecht S. S. Identification and mutagenicity of metabolites of 1-nitropyrene formed by rat liver. Cancer Res. 1983 Jul;43(7):3132–3137. [PubMed] [Google Scholar]
  9. El-Bayoumy K., Hecht S. S. Metabolism of 1-nitro[U-4,5,9,10-14C]pyrene in the F344 rat. Cancer Res. 1984 Oct;44(10):4317–4322. [PubMed] [Google Scholar]
  10. El-Bayoumy K., Hecht S. S., Sackl T., Stoner G. D. Tumorigenicity and metabolism of 1-nitropyrene in A/J mice. Carcinogenesis. 1984 Nov;5(11):1449–1452. doi: 10.1093/carcin/5.11.1449. [DOI] [PubMed] [Google Scholar]
  11. El-Bayoumy K., Sharma C., Louis Y. M., Reddy B., Hecht S. S. The role of intestinal microflora in the metabolic reduction of 1-nitropyrene to 1-aminopyrene in conventional and germfree rats and in humans. Cancer Lett. 1983 Jul;19(3):311–316. doi: 10.1016/0304-3835(83)90100-3. [DOI] [PubMed] [Google Scholar]
  12. Fu P. P., Chou M. W., Yang S. K., Beland F. A., Kadlubar F. F., Casciano D. A., Heflich R. H., Evans F. E. Metabolism of the mutagenic environmental pollutant, 6-nitrobenzo[a]pyrene: metabolic activation via ring oxidation. Biochem Biophys Res Commun. 1982 Apr 14;105(3):1037–1043. doi: 10.1016/0006-291x(82)91074-9. [DOI] [PubMed] [Google Scholar]
  13. Heflich R. H., Howard P. C., Beland F. A. 1-Nitrosopyrene: an intermediate in the metabolic activation of 1-nitropyrene to a mutagen in Salmonella typhimurium TA1538. Mutat Res. 1985 Mar;149(1):25–32. doi: 10.1016/0027-5107(85)90005-3. [DOI] [PubMed] [Google Scholar]
  14. Hirose M., Lee M. S., Wang C. Y., King C. M. Induction of rat mammary gland tumors by 1-nitropyrene, a recently recognized environmental mutagen. Cancer Res. 1984 Mar;44(3):1158–1162. [PubMed] [Google Scholar]
  15. Howard P. C., Beland F. A., Cerniglia C. E. Reduction of the carcinogen 1-nitropyrene to 1-aminopyrene by rat intestinal bacteria. Carcinogenesis. 1983 Aug;4(8):985–990. doi: 10.1093/carcin/4.8.985. [DOI] [PubMed] [Google Scholar]
  16. Howard P. C., Beland F. A. Xanthine oxidase catalyzed binding of 1-nitropyrene to DNA. Biochem Biophys Res Commun. 1982 Jan 29;104(2):727–732. doi: 10.1016/0006-291x(82)90697-0. [DOI] [PubMed] [Google Scholar]
  17. Howard P. C., Gerrard J. A., Milo G. E., Fu P. P., Beland F. A., Kadlubar F. F. Transformation of normal human skin fibroblasts by 1-nitropyrene and 6-nitrobenzo[a]pyrene. Carcinogenesis. 1983;4(3):353–355. doi: 10.1093/carcin/4.3.353. [DOI] [PubMed] [Google Scholar]
  18. Howard P. C., Heflich R. H., Evans F. E., Beland F. A. Formation of DNA adducts in vitro and in Salmonella typhimurium upon metabolic reduction of the environmental mutagen 1-nitropyrene. Cancer Res. 1983 May;43(5):2052–2058. [PubMed] [Google Scholar]
  19. King L. C., Jackson M., Ball L. M., Lewtas J. Binding of 1-nitro[14C]pyrene to DNA and protein in cultured lung macrophages and respiratory tissues. Cancer Lett. 1983 Jul;19(3):241–246. doi: 10.1016/0304-3835(83)90091-5. [DOI] [PubMed] [Google Scholar]
  20. King L. C., Kohan M. J., Ball L. M., Lewtas J. Mutagenicity of 1-nitropyrene metabolites from lung S9. Cancer Lett. 1984 Apr;22(3):255–262. doi: 10.1016/0304-3835(84)90160-5. [DOI] [PubMed] [Google Scholar]
  21. Kinouchi T., Manabe Y., Wakisaka K., Ohnishi Y. Biotransformation of 1-nitropyrene in intestinal anaerobic bacteria. Microbiol Immunol. 1982;26(11):993–1005. doi: 10.1111/j.1348-0421.1982.tb00249.x. [DOI] [PubMed] [Google Scholar]
  22. Kinouchi T., Ohnishi Y. Purification and characterization of 1-nitropyrene nitroreductases from Bacteroides fragilis. Appl Environ Microbiol. 1983 Sep;46(3):596–604. doi: 10.1128/aem.46.3.596-604.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kubitschek H. E., Williams D. M. Mutagenicity of fly ash from a fluidized-bed combuster during start-up and steady operating conditions. Mutat Res. 1980 Mar;77(3):287–291. doi: 10.1016/0165-1218(80)90063-4. [DOI] [PubMed] [Google Scholar]
  24. Li A. P., Dutcher J. S. Mutagenicity of mono-, di- and tri-nitropyrenes in Chinese hamster ovary cells. Mutat Res. 1983 Mar;119(3):387–392. doi: 10.1016/0165-7992(83)90190-2. [DOI] [PubMed] [Google Scholar]
  25. Lu C., McCalla D. R., McCarry B. E. The 1-nitropyrene reductase of Salmonella typhimurium. Chem Biol Interact. 1983 Jan;43(1):67–71. doi: 10.1016/0009-2797(83)90104-7. [DOI] [PubMed] [Google Scholar]
  26. Löfroth G., Hefner E., Alfheim I., Møoller M. Mutagenic activity in photocopies. Science. 1980 Aug 29;209(4460):1037–1039. doi: 10.1126/science.6996094. [DOI] [PubMed] [Google Scholar]
  27. Manabe Y., Kinouchi T., Wakisaka K., Tahara I., Ohnishi Y. Mutagenic 1-nitropyrene in wastewater from oil-water separating tanks of gasoline stations and in used crankcase oil. Environ Mutagen. 1984;6(5):669–681. doi: 10.1002/em.2860060505. [DOI] [PubMed] [Google Scholar]
  28. Maron D. M., Ames B. N. Revised methods for the Salmonella mutagenicity test. Mutat Res. 1983 May;113(3-4):173–215. doi: 10.1016/0165-1161(83)90010-9. [DOI] [PubMed] [Google Scholar]
  29. Marshall T. C., Royer R. E., Li A. P., Kusewitt D. F., Brooks A. L. Acute and genetic toxicity of 1-nitropyrene and its fate after single oral doses to rats. J Toxicol Environ Health. 1982 Sep;10(3):373–384. doi: 10.1080/15287398209530260. [DOI] [PubMed] [Google Scholar]
  30. McCoy E. C., Rosenkranz H. S. Cigarette smoking may yield nitroarenes. Cancer Lett. 1982 Jan;15(1):9–13. doi: 10.1016/0304-3835(82)90069-6. [DOI] [PubMed] [Google Scholar]
  31. Mermelstein R., Kiriazides D. K., Butler M., McCoy E. C., Rosenkranz H. S. The extraordinary mutagenicity of nitropyrenes in bacteria. Mutat Res. 1981 Jul;89(3):187–196. doi: 10.1016/0165-1218(81)90236-6. [DOI] [PubMed] [Google Scholar]
  32. Messier F., Lu C., Andrews P., McCarry B. E., Quilliam M. A., McCalla D. R. Metabolism of 1-nitropyrene and formation of DNA adducts in Salmonella typhimurium. Carcinogenesis. 1981;2(10):1007–1011. doi: 10.1093/carcin/2.10.1007. [DOI] [PubMed] [Google Scholar]
  33. Nachtman J. P., Wei E. T. Evidence for enzymatic reduction of 1-nitropyrene by rat liver fractions. Experientia. 1982 Jul 15;38(7):837–838. doi: 10.1007/BF01972302. [DOI] [PubMed] [Google Scholar]
  34. Nachtman J. P., Wolff S. Activity of nitro-polynuclear aromatic hydrocarbons in the sister chromatid exchange assay with and without metabolic activation. Environ Mutagen. 1982;4(1):1–5. doi: 10.1002/em.2860040102. [DOI] [PubMed] [Google Scholar]
  35. Nakayasu M., Sakamoto H., Wakabayashi K., Terada M., Sugimura T., Rosenkranz H. S. Potent mutagenic activity of nitropyrenes on Chinese hamster lung cells with diphtheria toxin resistance as a selective marker. Carcinogenesis. 1982;3(8):917–922. doi: 10.1093/carcin/3.8.917. [DOI] [PubMed] [Google Scholar]
  36. Narai N., Kitamura S., Tatsumi K. A comparative study on 1-nitropyrene and nitrofurazone reductases in Escherichia coli. J Pharmacobiodyn. 1984 Jun;7(6):407–413. doi: 10.1248/bpb1978.7.407. [DOI] [PubMed] [Google Scholar]
  37. Ohgaki H., Matsukura N., Morino K., Kawachi T., Sugimura T., Morita K., Tokiwa H., Hirota T. Carcinogenicity in rats of the mutagenic compounds 1-nitropyrene and 3-nitrofluoranthene. Cancer Lett. 1982 Jan;15(1):1–7. doi: 10.1016/0304-3835(82)90068-4. [DOI] [PubMed] [Google Scholar]
  38. Pitts J. N., Jr, Van Cauwenberghe K. A., Grosjean D., Schmid J. P., Fitz D. R., Belser W. L., Knudson G. P., Hynds P. M. Atmospheric reactions of polycyclic aromatic hydrocarbons: facile formation of mutagenic nitro derivatives. Science. 1978 Nov 3;202(4367):515–519. doi: 10.1126/science.705341. [DOI] [PubMed] [Google Scholar]
  39. Rosenkranz H. S. Direct-acting mutagens in diesel exhausts: magnitude of the problem. Mutat Res. 1982 Mar;101(1):1–10. doi: 10.1016/0165-1218(82)90159-8. [DOI] [PubMed] [Google Scholar]
  40. Rosenkranz H. S., McCoy E. C., Sanders D. R., Butler M., Kiriazides D. K., Mermelstein R. Nitropyrenes: isolation, identificaton, and reduction of mutagenic impurities in carbon black and toners. Science. 1980 Aug 29;209(4460):1039–1043. doi: 10.1126/science.6996095. [DOI] [PubMed] [Google Scholar]
  41. Salmeen I., Durisin A. M., Prater T. J., Riley T., Schuetzle D. Contribution of 1-nitropyrene to direct-acting Ames assay mutagenicities of diesel particulate extracts. Mutat Res. 1982 Apr;104(1-3):17–23. doi: 10.1016/0165-7992(82)90114-2. [DOI] [PubMed] [Google Scholar]
  42. Salmeen I., Zacmanidis P., Ball J. 1-Nitropyrene reduction by Salmonella typhimurium, V79 Chinese hamster and primary rat liver cells. Mutat Res. 1983 Oct;122(1):23–28. doi: 10.1016/0165-7992(83)90137-9. [DOI] [PubMed] [Google Scholar]
  43. Warner U. The serious import of humour in health visiting. J Adv Nurs. 1984 Jan;9(1):83–87. doi: 10.1111/j.1365-2648.1984.tb00347.x. [DOI] [PubMed] [Google Scholar]

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