The disposition of polychlorinated biphenyls (PCBs) differs between germ-free and conventional mice.

Xueshu Li, Joe Jongpyo Lim, Kai Wang, Bhagwat Prasad, Deepak K Bhatt, Julia Yue Cui, Hans-Joachim Lehmler
Author Information
  1. Xueshu Li: Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA.
  2. Joe Jongpyo Lim: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA.
  3. Kai Wang: Department of Biostatistics, University of Iowa, Iowa City, IA 52242, USA.
  4. Bhagwat Prasad: Department of Pharmaceutics, University of Washington, Seattle, WA 98105, USA.
  5. Deepak K Bhatt: Department of Pharmaceutics, University of Washington, Seattle, WA 98105, USA.
  6. Julia Yue Cui: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA.
  7. Hans-Joachim Lehmler: Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA. Electronic address: hans-joachim-lehmler@uiowa.edu.

Abstract

The disposition of toxicants, such as polychlorinated biphenyls (PCBs), in germ-free (GF) vs. conventional (CV) mice has received little attention to date. Here, we investigate PCB levels in three-month-old female CV and GF mice exposed orally daily for 3 days to 0, 6, or 30 mg/kg body weight of the Fox River Mixture (FRM), an environmental PCB mixture. We euthanized animals 24 h after the final dose. PCB profiles in tissues differed from the FRM profile but were similar in tissues across all 4 PCB exposure groups. PCB levels in CV but not GF mice followed the difference in PCB dose. Importantly, PCB levels were higher in CV than GF mice exposed to the same dose. Hepatic cytochrome P450 enzyme or lipid levels did not explain these trends in PCB tissue levels. Thus, toxicity studies with CV and GF animals need to assess the toxicokinetics of the toxicant investigated. CAPSULE: PCB levels are typically higher in conventional than germ-free mice exposed to the same dose of PCBs.

Keywords

References

  1. Environ Sci Technol. 2005 May 15;39(10):3513-20 [PMID: 15954224]
  2. Environ Sci Technol. 2012 Sep 4;46(17):9653-62 [PMID: 22846166]
  3. Biochemistry. 1981 Dec 22;20(26):7379-84 [PMID: 6798990]
  4. Toxicology. 2017 Sep 1;390:124-134 [PMID: 28890136]
  5. Drug Metab Dispos. 1978 Sep-Oct;6(5):584-90 [PMID: 30609]
  6. Environ Sci Pollut Res Int. 2018 Jun;25(17):16508-16521 [PMID: 29322390]
  7. Environ Int. 2010 Nov;36(8):884-92 [PMID: 19923000]
  8. Environ Pollut. 2018 Jun;237:473-486 [PMID: 29518658]
  9. Toxicol Rep. 2021 Mar 10;8:536-547 [PMID: 33777700]
  10. Drug Metab Dispos. 2005 Oct;33(10):1466-76 [PMID: 16006569]
  11. Environ Toxicol Pharmacol. 2022 May;92:103854 [PMID: 35331926]
  12. Science. 2019 Feb 8;363(6427): [PMID: 30733391]
  13. Science. 1982 Aug 13;217(4560):645-7 [PMID: 6806905]
  14. Curr Opin Pharmacol. 2019 Dec;49:6-10 [PMID: 31051390]
  15. Environ Pollut. 2021 Jan 1;268(Pt A):115726 [PMID: 33032095]
  16. Saudi Pharm J. 2019 Dec;27(8):1146-1156 [PMID: 31885474]
  17. Environ Pollut. 2020 Nov;266(Pt 1):115233 [PMID: 32712482]
  18. Curr Pharmacol Rep. 2019 Dec;5(6):481-490 [PMID: 33312848]
  19. Environ Sci Technol. 2015 Jan 6;49(1):616-25 [PMID: 25420130]
  20. J Lipid Res. 2010 May;51(5):1101-12 [PMID: 20040631]
  21. Anal Biochem. 2003 Mar 1;314(1):149-52 [PMID: 12633615]
  22. Sci Total Environ. 2019 Feb 25;653:274-282 [PMID: 30412872]
  23. Toxicology. 1984 Jun;31(3-4):191-206 [PMID: 6330936]
  24. Environ Pollut. 2018 Nov;242(Pt A):1022-1032 [PMID: 30373033]
  25. Environ Health Perspect. 2009 Mar;117(3):426-35 [PMID: 19337518]
  26. Environ Health Perspect. 2013 Jun;121(6):725-30 [PMID: 23632211]
  27. Genome Biol. 2014;15(12):550 [PMID: 25516281]
  28. Environ Sci Technol. 2012 Oct 16;46(20):11393-401 [PMID: 22974126]
  29. Gut Microbes. 2020 May 3;11(3):587-596 [PMID: 31564204]
  30. Chem Biol Interact. 1981 Apr;35(1):1-12 [PMID: 6781768]
  31. J Agric Food Chem. 1999 Jul;47(7):2898-903 [PMID: 10552583]
  32. Toxicol Appl Pharmacol. 1998 Dec;153(2):199-210 [PMID: 9878591]
  33. Chem Res Toxicol. 2013 Nov 18;26(11):1642-51 [PMID: 24107130]
  34. Toxicol Sci. 2018 Dec 01;166(2):269-287 [PMID: 30496569]
  35. Sci Total Environ. 2021 Sep 15;787:147677 [PMID: 34004538]
  36. Environ Sci Technol. 2015 Oct 6;49(19):11875-83 [PMID: 26348937]
  37. Comp Biochem Physiol C Comp Pharmacol Toxicol. 1993 May;105(1):95-106 [PMID: 8101795]
  38. Chirality. 2007 Jan;19(1):56-66 [PMID: 17089340]
  39. Toxicol Sci. 2014 Aug 1;140(2):283-97 [PMID: 24812009]
  40. Drug Metab Dispos. 2005 Mar;33(3):373-80 [PMID: 15608140]
  41. J Biol Chem. 1983 May 10;258(9):5967-76 [PMID: 6304102]
  42. J Biol Chem. 2002 Aug 30;277(35):31994-2002 [PMID: 12077151]
  43. Environ Epidemiol. 2019 Feb;3(1): [PMID: 30778401]
  44. Nucleic Acids Res. 2018 Jul 2;46(W1):W486-W494 [PMID: 29762782]
  45. Xenobiotica. 1991 Apr;21(4):433-45 [PMID: 1897243]
  46. Environ Pollut. 2019 Oct;253:708-721 [PMID: 31336350]
  47. Toxicol Sci. 2005 Dec;88(2):400-11 [PMID: 16177234]
  48. Environ Pollut. 2018 Aug;239:332-341 [PMID: 29674211]
  49. ILAR J. 2015;56(2):241-9 [PMID: 26323633]
  50. FASEB J. 2010 Dec;24(12):4948-59 [PMID: 20724524]
  51. J Nutr Biochem. 1990 Jul;1(7):350-4 [PMID: 15539224]
  52. Arch Environ Contam Toxicol. 2008 Oct;55(3):510-7 [PMID: 18437444]
  53. Toxicol Sci. 2020 Sep 1;177(1):168-187 [PMID: 32544245]
  54. Br J Clin Pharmacol. 2015 Feb;79(2):241-53 [PMID: 25125025]
  55. Regul Toxicol Pharmacol. 2021 Mar;120:104842 [PMID: 33346014]
  56. J Biol Chem. 1951 Nov;193(1):265-75 [PMID: 14907713]
  57. Toxicology. 2012 Dec 8;302(1):25-33 [PMID: 22824115]
  58. Drug Metab Dispos. 2017 Nov;45(11):1197-1214 [PMID: 28864748]
  59. Toxicol Sci. 2015 Sep;147(1):84-103 [PMID: 26032512]
  60. Biopharm Drug Dispos. 2020 Jul;41(7):275-282 [PMID: 32562497]

Grants

  1. P30 ES005605/NIEHS NIH HHS
  2. P50 HD103524/NICHD NIH HHS
  3. R01 ES031098/NIEHS NIH HHS
  4. P20 GM103418/NIGMS NIH HHS
  5. R01 GM111381/NIGMS NIH HHS
  6. P30 ES007033/NIEHS NIH HHS
  7. R01 ES025708/NIEHS NIH HHS
  8. T32 ES007032/NIEHS NIH HHS
  9. R01 ES019487/NIEHS NIH HHS
  10. P42 ES013661/NIEHS NIH HHS
  11. R01 ES014901/NIEHS NIH HHS

MeSH Term

Animals
Female
Liver
Mice
Polychlorinated Biphenyls

Chemicals

Polychlorinated Biphenyls

Word Cloud

Created with Highcharts 10.0.0PCBlevelsmiceGFCVdosePCBsgerm-freeconventionalexposeddispositionpolychlorinatedbiphenylsFRManimalsprofilestissueshigherHepaticlipidtoxicantsvsreceivedlittleattentiondateinvestigatethree-month-oldfemaleorallydaily3days0630 mg/kgbodyweightFoxRiverMixtureenvironmentalmixtureeuthanized24 hfinaldifferedprofilesimilaracross4exposuregroupsfolloweddifferenceImportantlycytochromeP450enzymeexplaintrendstissueThustoxicitystudiesneedassesstoxicokineticstoxicantinvestigatedCAPSULE:typicallydiffersDispositionDose-responsecongenerhomologsSimilaritycoefficient

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