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Sonoda J, Seki Y, Hakura A, et al. Time course of the incidence/multiplicity and histopathological features of murine colonic dysplasia, adenoma and adenocarcinoma induced by benzo[a]pyrene and dextran sulfate sodium. J Toxicol Pathol. 2015;28(2):109-20doi: 10.1293/tox.2014-0061.
Sonoda, J., Seki, Y., Hakura, A., & Hosokawa, S. (2015). Time course of the incidence/multiplicity and histopathological features of murine colonic dysplasia, adenoma and adenocarcinoma induced by benzo[a]pyrene and dextran sulfate sodium. Journal of toxicologic pathology, 28(2), 109-20. https://doi.org/10.1293/tox.2014-0061
Sonoda, Jiro, et al. "Time course of the incidence/multiplicity and histopathological features of murine colonic dysplasia, adenoma and adenocarcinoma induced by benzo[a]pyrene and dextran sulfate sodium." Journal of toxicologic pathology vol. 28,2 (2015): 109-20. doi: https://doi.org/10.1293/tox.2014-0061
Sonoda J, Seki Y, Hakura A, Hosokawa S. Time course of the incidence/multiplicity and histopathological features of murine colonic dysplasia, adenoma and adenocarcinoma induced by benzo[a]pyrene and dextran sulfate sodium. J Toxicol Pathol. 2015 Apr;28(2):109-20. doi: 10.1293/tox.2014-0061. Epub 2015 Mar 01. PMID: 26028820; PMCID: PMC4444509.
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J Toxicol Pathol. 2015 Apr;28(2):109-20. doi: 10.1293/tox.2014-0061. Epub 2015 Mar 01.

Time course of the incidence/multiplicity and histopathological features of murine colonic dysplasia, adenoma and adenocarcinoma induced by benzo[a]pyrene and dextran sulfate sodium.

Journal of toxicologic pathology

Jiro Sonoda, Yuki Seki, Atsushi Hakura, Satoru Hosokawa

Affiliations

  1. Tsukuba Drug Safety, Global Drug Safety, Biopharmaceutical Assessments Core Function Unit, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan.

PMID: 26028820 PMCID: PMC4444509 DOI: 10.1293/tox.2014-0061

Abstract

Benzo[a]pyrene (BP) is mutagenic but noncarcinogenic in the murine colon. Recently, we reported rapid induction of colonic tumors by treatment of CD2F1 mice with BP (125 mg/kg for 5 days) followed by a colitis inducer, dextran sulfate sodium (DSS) (4% in drinking water for 1 or 2 weeks). However, there are no reports on detailed time course and histopathological features of colonic proliferative lesions in this model. Here, we show the detailed time course of colonic dysplasia, adenoma and adenocarcinoma induced by treatment with BP, DSS, and a combination of the two (BP/DSS). In the colon of mice exposed to BP/DSS, 14.6 dysplastic foci per mouse were present one week after DSS treatment (week 4). The number of dysplastic foci decreased with time to 3.1 at week 9 and thereafter remained almost constant. At week 4, 1.5 adenocarcinomas were also observed, with a marked increase in numbers with time, reaching 29.3 at week 14. In contrast, the number of dysplastic foci induced by DSS alone showed a time course similar to that following BP/DSS treatment; however, only a few tumors appeared. Neither dysplastic foci nor neoplastic lesions were induced by BP only. In mice exposed to BP/DSS, β-catenin was demonstrated immunohistochemically in the nucleus and/or cytoplasm of the tumor cells, and this translocation from the cell membrane was evident in subsets of dysplastic foci. In dysplastic foci induced by DSS alone, β-catenin was absent in the nucleus/cytoplasm. These finding suggest that aberrant β-catenin accumulation in dysplastic foci is associated with tumor progression in this BP/DSS model.

Keywords: benzo[a]pyrene; colon; dextran sulfate sodium; dysplastic foci; tumor; β-catenin

References

  1. J Carcinog. 2009;8:5 - PubMed
  2. Carcinogenesis. 2003 Jan;24(1):91-7 - PubMed
  3. Carcinogenesis. 2000 Apr;21(4):757-68 - PubMed
  4. Cancer Sci. 2004 Oct;95(10):792-7 - PubMed
  5. Oncogene. 2007 May 24;26(24):3511-20 - PubMed
  6. Mutat Res. 1999 May 3;426(1):71-7 - PubMed
  7. J Gastroenterol Hepatol. 2002 Oct;17(10):1078-83 - PubMed
  8. Cancer Lett. 2003 Aug 20;198(2):145-52 - PubMed
  9. Mutat Res. 1999 Jul 15;443(1-2):139-47 - PubMed
  10. Carcinogenesis. 2006 Jan;27(1):162-9 - PubMed
  11. Dig Surg. 2005;22(1-2):16-25 - PubMed
  12. Carcinogenesis. 2003 Jun;24(6):1015-9 - PubMed
  13. Toxicol Pathol. 2009 Dec;37(7):938-46 - PubMed
  14. Cell Prolif. 2005 Dec;38(6):387-405 - PubMed
  15. Lab Invest. 1974 Apr;30(4):505-13 - PubMed
  16. Cancer Sci. 2004 Sep;95(9):721-7 - PubMed
  17. Food Chem Toxicol. 2011 Nov;49(11):2997-3001 - PubMed
  18. Nature. 2011 Jan 20;469(7330):415-8 - PubMed
  19. Cancer Sci. 2003 Nov;94(11):965-73 - PubMed
  20. J Toxicol Pathol. 2013 Dec;26(4):335-41 - PubMed
  21. Gut. 2004 Jun;53(6):899-910 - PubMed
  22. Cancer Res. 2000 Jul 1;60(13):3323-7 - PubMed
  23. Mutat Res. 1998 Feb 26;398(1-2):123-30 - PubMed
  24. World J Gastroenterol. 2004 Oct 15;10(20):2958-62 - PubMed
  25. Carcinogenesis. 2005 Jan;26(1):229-38 - PubMed
  26. Acta Pharmacol Sin. 2007 Sep;28(9):1450-9 - PubMed
  27. Carcinogenesis. 1998 Jan;19(1):117-24 - PubMed
  28. Carcinogenesis. 2009 Feb;30(2):183-96 - PubMed
  29. Cell. 2002 Oct 18;111(2):241-50 - PubMed
  30. Comp Med. 2000 Feb;50(1):16-26 - PubMed
  31. Mutat Res. 2010 Jul-Sep;705(1):40-59 - PubMed
  32. IARC Monogr Eval Carcinog Risks Hum. 2010;92 :1-853 - PubMed
  33. Nutr Cancer. 1984;6(2):92-7 - PubMed
  34. Mutat Res. 2004 May;566(3):191-208 - PubMed
  35. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2011 Oct;29(4):324-57 - PubMed
  36. Hum Pathol. 1983 Nov;14 (11):931-68 - PubMed
  37. Nat Cell Biol. 2005 Apr;7(4):381-6 - PubMed
  38. Cancer Sci. 2007 Jan;98(1):6-10 - PubMed
  39. Am J Pathol. 2003 Oct;163(4):1607-14 - PubMed
  40. Carcinogenesis. 2007 Oct;28(10):2199-206 - PubMed
  41. Food Chem Toxicol. 2010 Jan;48 Suppl 1:S42-8 - PubMed
  42. Hum Pathol. 1994 Nov;25(11):1160-71 - PubMed

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