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Toxins 2012, 4(9), 643-662; doi:10.3390/toxins4090643
Article

Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression

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Received: 20 June 2012; in revised form: 20 August 2012 / Accepted: 21 August 2012 / Published: 11 September 2012
(This article belongs to the Special Issue Ochratoxins 2011-2012)
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Abstract: Ochratoxin A (OTA) is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the mammalian target of rapamycin, which is a serine/threonine kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6 expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human angiosarcoma were negative for p-S6. The combined findings are reminiscent of constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not obviously mimic human urinary tract tumourigenesis.
Keywords: ochratoxin A; phospho-S6 ribosomal protein; mycotoxin; renal cell carcinoma; transitional cell carcinoma; testicular cancer; angiosarcoma; Balkan endemic nephropathy; food safety; DNA adducts ochratoxin A; phospho-S6 ribosomal protein; mycotoxin; renal cell carcinoma; transitional cell carcinoma; testicular cancer; angiosarcoma; Balkan endemic nephropathy; food safety; DNA adducts
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Gazinska, P.; Herman, D.; Gillett, C.; Pinder, S.; Mantle, P. Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression. Toxins 2012, 4, 643-662.

AMA Style

Gazinska P, Herman D, Gillett C, Pinder S, Mantle P. Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression. Toxins. 2012; 4(9):643-662.

Chicago/Turabian Style

Gazinska, Patrycja; Herman, Diana; Gillett, Cheryl; Pinder, Sarah; Mantle, Peter. 2012. "Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression." Toxins 4, no. 9: 643-662.



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