Changes of biomarkers with oral exposure to benzo(a)pyrene, phenanthrene and pyrene in rats

Kang, Hwan-Goo;Jeong, Sang-Hee;Cho, Myung-Haing;Cho, Joon-Hyoung

  • Published : 20071200

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants present in air and food. Among PAHs, benzo(a)pyrene(BaP), phenanthrene (PH) and pyrene (PY) are considered to be important for their toxicity or abundance. To investigate the changes of biomarkers after PAH exposure, rats were treated with BaP (150 μg/kg) alone or with PH (4,300 μg/kg) and PY (2,700 μg/kg) (BPP group) by oral gavage once per day for 30 days. 7-ethoxyresorufin-O-deethylase activity in liver microsomal fraction was increased in only BaP groups. The highest concentration (34.5 ng/g) of BaP, was found in muscle of rats treated with BaP alone at 20 days of treatment; it was 23.6 ng/g in BPP treated rats at 30 days of treatment. The highest PH concentration was 47.1 ng/g in muscle and 118.8 ng/g in fat, and for PY it was 29.7 ng/g in muscle and 219.9 ng/g in fat, in BPP groups. In urine, 114-161 ng/ml 3-OH-PH was found, while PH was 41-69 ng/ml during treatment. 201-263 ng/ml 1-OH-PY was found, while PH was 9-17 ng/ml in urine. The level of PY, PH and their metabolites in urine was rapidly decreased after withdrawal of treatment. This study suggest that 1-OH-PY in urine is a sensitive biomarker for PAHs; it was the most highly detected marker among the three PAHs and their metabolites evaluated during the exposure period and for 14 days after withdrawal.

Keywords

References

  1. Alexandrov K, Rojas M, Geneste O, Castegnaro M, Camus AM, Petruzzelli S, Giuntini C, Bartsch H. An improved fluorometric assay for dosimetry of benzo(a)pyrene diol-epoxide-DNA adducts in smokers' lung: comparisons with total bulky adducts and aryl hydrocarbon hydroxylase activity. Cancer Res 1992, 52, 6248-6253
  2. Arfsten DP, Schaeffer DJ, Muneny DC. The effects of near ultraviolet radiation on the toxic effects of polycyclic aromatic hydrocarbons in animals and plants: a review. Ecotoxicol Environ Saf 1996, 33, 1-24 https://doi.org/10.1006/eesa.1996.0001
  3. Arif JM, Shappell N, Sikka HC, Kumar S, Gupta RC. $^{32}PPostlabeling$ analysis of lipophilic DNA adducts resulting from interaction with $({\pm})$-3-hydroxy-trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene. Chem Biol Interact 1999, 118, 87-97 https://doi.org/10.1016/S0009-2797(98)00116-1
  4. Bosveld ATC, de Bie PAF, van den Brink NW, Jongepier H, Klomp AV. In vitro EROD induction equivalency factor for the 10 PAHs generally monitored in risk assessment studies in the Netherlands. Chemosphere 2002, 49, 75-83 https://doi.org/10.1016/S0045-6535(02)00161-3
  5. Buchet JP, Gennart JP, Mercado-Calderon F, Delavignette JP, Cupers L, Lauwerys R. Evaluation of exposure to polycyclic aromatic hydrocarbons in a coke production and a graphite electrode manufacturing plant: assessment of urinary excretion of 1-hydroxypyrene as a biological indicator of exposure. Br J Ind Med 1992, 49, 761-768
  6. Buckley TJ, Loiy PJ. An examination of the time course from human dietary exposure to polycyclic aromatic hydrocarbons to urinary elimination of 1-hydroxypyrene. Br J Ind Med 1992, 49, 113-124
  7. Bulter JP, Post GB, Lioy PJ, Waldman JM, Greenberg A. Assessment of carcinogenic risk from personal exposure to benzo(a)pyrene in the total human environmental exposure study (THEES). Air Waste 1993, 43, 970-977 https://doi.org/10.1080/1073161X.1993.10467179
  8. Burke MD, Thompson S, Elcombe CR, Halpert J, Haaparanta T, Mayer RT. Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P-450. Biochem Pharmacol 1985, 34, 3337-3345 https://doi.org/10.1016/0006-2952(85)90355-7
  9. Chen BH, Wang CY, Chiu CP. Evaluation of analysis of polycyclic aromatic hydrocarbons in meat products by liquid chromatography. J Agric Food Chem 1996, 44, 2244-2251 https://doi.org/10.1021/jf9508211
  10. Dennis MJ, Massey RC, Cripps G, Venn I, Howarth N, Lee G. Factors affecting the polycyclic aromatic hydrocarbon content of cereals, fats and other food products. Food Addit Contam 1991, 8, 517-530 https://doi.org/10.1080/02652039109374004
  11. Easton MPL, Luszinak D, Geest EV. Preliminary examination of contaminant loadings in farmed salmon, wild salmon and commercial salmon feed. Chemosphere 2002, 46, 1053-1074 https://doi.org/10.1016/S0045-6535(01)00136-9
  12. Fouchecourt MO, Berny P, Riviere JL. Bioavailability of PCBs to male laboratory rats maintained on litters of contaminated soils: PCB burden and induction of alkoxyresorufin O-dealkylase activities in liver and lung. Arch Environ Contam Toxicol 1998, 35, 680-687 https://doi.org/10.1007/s002449900431
  13. Godschalk RWL, Verner ITM, Kriek E, Floot B, Schilderman PAEL, Moonen EJC, Kleinjans JCS, van Schooten FJ. Comparison of $^{32}P$-postlabeling and HPLCFD analysis of DNA adduct in rat acutely exposed to benzo(a)pyrene. Chem Biol Interact 1997, 104, 41-54 https://doi.org/10.1016/S0009-2797(97)03765-4
  14. Graslund A, Jernstrom B. DNA-carcinogen interaction: covalent DNA-adducts of benzo(a)pyrene 7,8-dihydrodiol-9,10-epoxides studied by biochemical and biophysical techniques. Q Rev Biophys 1989, 22, 1-37 https://doi.org/10.1017/S0033583500002973
  15. Gravato C, Santos MA. Juvenile sea bass liver P450, EROD induction, and erythrocytic genotoxic responses to PAH and PAH-like compounds. Ecotoxicol Environ Saf 2002, 51, 115-127 https://doi.org/10.1006/eesa.2001.2133
  16. Gundel J, Schaller KH, Angerer J. Occupational exposure to polycyclic aromatic hydrocarbons in a fireproof stone producing plant: biological monitoring of 1-hydroxypyrene, 1-,2-, 3- and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)pyrene. Int Arch Occup Environ Health 2000, 73, 270-274 https://doi.org/10.1007/s004200050427
  17. Hansen AM, Poulsen OM, Christensen JM. Determination of 1-hydroxypyrene in human urine by HPLC. J Anal Toxicol 1993, 17, 38-41 https://doi.org/10.1093/jat/17.1.38
  18. IARC. IARC Monographs on the Evaluation of Carcinogenic Risk to Human. Vol. 32, p. 211, IARC, Lyon, 1983
  19. Islam GA, Greibrok T, Harvey RG, Overebo S. HPLC analysis of benzo[a]pyrene-albumin adducts in benzo[a]pyrene exposed rats. Detection of cis-tetrols arising from hydrolysis of adducts of anti- and syn-BPDE III with proteins. Chem Biol Interact 1999, 123, 133-148 https://doi.org/10.1016/S0009-2797(99)00129-5
  20. Jacob J, Grimmer G. Metabolism and excretion of polycyclic aromatic hydrocarbons in rat and in human. Cent Eur J Public Health 1996, 4, 33-39
  21. Jongeneelen FJ, Akker WVD, Bos RP, Anzion RBM, Theuws JLG, Roelofs HMJ, Henderson PTH. 1-OH-pyrene as an indicator of mutagenicity of coal tar after activation with human liver preparation. Mutat Res 1988, 204, 195-201 https://doi.org/10.1016/0165-1218(88)90089-4
  22. Jongeneelen FJ, Anizon RBM, Scheepers PTJ. 1-hydroxypyrene in urine as a biological indicator of exposure to polycyclic aromatic hydrocarbons in several work environments. Ann Occup Hyg 1988, 32, 35-43 https://doi.org/10.1093/annhyg/32.1.35
  23. Jongeneelen FJ. Benchmark guideline for urinary 1- as biomarker of occupational exposure to polycyclic aromatic hydrocarbon. Ann Occup Hyg 2001, 45, 3-13 https://doi.org/10.1016/S0003-4878(00)00009-0
  24. Kazerouni N, Shinha R, Hsu CH, Greenberg A, Rothman N. Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study. Food Chem Toxicol 2001, 39, 423-436 https://doi.org/10.1016/S0278-6915(00)00158-7
  25. Keimig SD, Kiby KW, Morgna PP. Identification of 1-hydroxypyrene as a major metabolite of pyrene in pig urine. Xenobiotica 1983, 13, 415-420 https://doi.org/10.3109/00498258309052279
  26. Marczynski B, Rihs HP, Rossbach B, Holzer J, Angerer J, Scherenberg M, Hoffmann G, Bruning T, Wilhelm M. Analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine and DNA strand breaks in white blood cells of occupationally exposed workers: comparison with ambient monitoring, urinary metabolites and enzyme polymorphisms. Carcinogenesis 2002, 23, 273-281 https://doi.org/10.1093/carcin/23.2.273
  27. Mitchell CE, Tu KW. Distribution, retention, and elimination of pyrene in rats after inhalation. J Toxicol Environ Health 1979, 5, 1171-1179 https://doi.org/10.1080/15287397909529822
  28. Moorthy B, Sriram P, Randerath K. Chemical structures and time-dependent effects of polycyclic aromatic hydrocarbon-type inducers on rat liver cytochrome P450, DNA adducts, and I-compounds. Fundamental Appl Toxicol 1994, 22, 549-560 https://doi.org/10.1006/faat.1994.1062
  29. Nilsen A, Tronnes T, Westerholm R, Rannug U, Nilsen OG, Helleberg H, Kautiainen A, Hedenskog M, Tornqvist M. Short term exposure of rodent to disel exhausts; usefulness for studies of genotoxic and immunotoxic effect. Chem Biol Interact 1999, 118, 19-38 https://doi.org/10.1016/S0009-2797(98)00114-8
  30. Nisbet ICT, LaGoy PK. Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons. Regul Toxicol Pharmacol 1992, 16, 290-300 https://doi.org/10.1016/0273-2300(92)90009-X
  31. Ovrebo S, Haugen A, Fjeldstad PE, Hemminkj K, Szyfter, K. Biological monitoring of exposure to polycyclic aromatic hydrocarbon in an electrode paste plant. J Occup Med 1994, 36, 303-310 https://doi.org/10.1097/00043764-199403000-00007
  32. Park SS, Kim YJ, Kang CH. Atomospheric polycyclic aromatic hydrocarbons in Seoul, Korea. Atmos Environ 2002, 36, 2917-2924 https://doi.org/10.1016/S1352-2310(02)00206-6
  33. Parvanello S, Zanesi N, Levis AG. BaP metabolism and DNA -adduct formation in cultured human lymphocytes treated in vitro with BaP and BaP-7,8-dihydrodiol. ATLA 1992, 20, 126-137
  34. Pavanello S, Favretto D, Brugnone F, Mastrangelo G, Dal Pra G, Clonfero E. HPLC/fluorescence determination of anti-BPDE-DNA adducts in mononuclear white blood cells from PAH-exposed humans. Carcinogenesis 1999, 20, 431-435 https://doi.org/10.1093/carcin/20.3.431
  35. Pohl RJ, Fouts JR. A rapid method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular fraction. Anal Biochem 1980, 107, 150-155 https://doi.org/10.1016/0003-2697(80)90505-9
  36. Rojas M, Alexandrov K, von Schooten FS, Hillebrand M, Kriek E, Barstch H. Validation of a new fluorimetric assay for benzo[a]pyrene diolepoxide-DNA adducts in human white blood cells: comparisons with 32P-postlabeling and ELISA. Carcinogenesis 1995, 15, 557-560 https://doi.org/10.1093/carcin/15.3.557
  37. Roos PH, Tschirbs S, Pfeifer F, Welge P, Hack A, Wilhelm M, Bolt HM. Risk potentials for humans of original and remediated PAH-contaminated soils: application of biomarkers of effect. Toxicology 2004, 205, 181-194 https://doi.org/10.1016/j.tox.2004.06.050
  38. Roos PH, van Afferden M, Strotkamp D, Tappe D, Pfeifer F, Hanstein WG. Liver microsomal levels of cytochrome P450IA1 as biomarker for exposure and bioavailability of soil-bound polycyclic aromatic hydrocarbons. Arch Environ Contam Toxicol 1996, 30, 107-113 https://doi.org/10.1007/BF00211335
  39. Saunders CR, Ramesh A, Shockley DC. Modulation of neurotoxic behavior in F-344 rats by temporal disposition of benzo(a)pyrene. Toxicol Lett 2002, 129, 33-45 https://doi.org/10.1016/S0378-4274(01)00467-2
  40. Sjogren M, Ehrenbrg L, Rannug U. Relevance of different biological assays in assessing initiating and promoting properties of polycyclic aromatic hydrocarbons with respect to carcinogenic potency. Mutat Res 1996, 358, 97-112 https://doi.org/10.1016/0027-5107(96)00175-3
  41. WHO. Evaluation of Certain Food Additives and Contaminants; Benzo(a)pyrene. WHO Food Additives Series 28. pp. 27-29, WHO, Geneva, 1998
  42. Willett KL, Wassenberg D, Lienesch L, Reichert W, Di Giulio RT. In vivo and in vitro inhibition of CYP1A-dependent activity in Fundulus heteroclitus by the polynuclear aromatic hydrocarbon fluoranthene. Toxicol Appl Pharmacol 2001, 177, 264-271 https://doi.org/10.1006/taap.2001.9296
  43. Withey JR, Law FC, Endrenyi L. Pharmacokinetics and bioavailability of pyrene in the rat. J Toxicol Environ Health 1991, 32, 429-447 https://doi.org/10.1080/15287399109531494
  44. Yamaguchi K, Near R, Shneider A, Cui H, Ju ST, Sherr DH. Fluoranthecene-induced apoptosis in murine T cell hybridomas is independent of the aromatic hydrocarbon receptor. Toxicol Appl Pharmacol 1996, 139, 144-152 https://doi.org/10.1006/taap.1996.0153