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Comparative immunohistochemical analysis of ochratoxin A tumourigenesis in rats and urinary tract carcinoma in humans; mechanistic significance of p-S6 ribosomal protein expression.

Gazinska P, Herman D, Gillett C, Pinder S, Mantle P - Toxins (Basel) (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Breakthrough Breast Cancer Research Unit, Guy's Hospital, King's Health Partners AHSC, King's College London School of Medicine, London SE1 9RT, UK. patrycja.gazinska@kcl.ac.uk

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.

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Related in: MedlinePlus

Recognition of OTA carcinogenicity in rats. (A) (case 17), H & E stained section of small in situ renal carcinoma (left), matched with position (magnified) of tumour edge elements stained intensely for p-S6 protein in another section from the same block; (B) (case 12, also Figure 4), renal tumour edge (above), stained for p-S6, contrasting with unstained stretched kidney cortex with distorted glomerulus (below); (C) (case 3), carcinoma, intensely stained for p-S6 into regions of kidney sectioned through the papilla (top right); (D) (case 1), lung tissue, from rat with renal carcinoma, showing scattered intensely-stained elements, more clearly seen in magnified region and attributed to metastatic fragments from primary renal tumour.
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toxins-04-00643-f002: Recognition of OTA carcinogenicity in rats. (A) (case 17), H & E stained section of small in situ renal carcinoma (left), matched with position (magnified) of tumour edge elements stained intensely for p-S6 protein in another section from the same block; (B) (case 12, also Figure 4), renal tumour edge (above), stained for p-S6, contrasting with unstained stretched kidney cortex with distorted glomerulus (below); (C) (case 3), carcinoma, intensely stained for p-S6 into regions of kidney sectioned through the papilla (top right); (D) (case 1), lung tissue, from rat with renal carcinoma, showing scattered intensely-stained elements, more clearly seen in magnified region and attributed to metastatic fragments from primary renal tumour.

Mentions: The following descriptions of immunohistochemical findings in tissues are best read in conjunction with rat case context detail and literature cross-referencing tabulated in Supplementary Data. Findings are also summarised in Table 1 and illustrated in Figure 1, Figure 2, Figure 3, Figure 4.


Comparative immunohistochemical analysis of ochratoxin A tumourigenesis in rats and urinary tract carcinoma in humans; mechanistic significance of p-S6 ribosomal protein expression.

Gazinska P, Herman D, Gillett C, Pinder S, Mantle P - Toxins (Basel) (2012)

Recognition of OTA carcinogenicity in rats. (A) (case 17), H & E stained section of small in situ renal carcinoma (left), matched with position (magnified) of tumour edge elements stained intensely for p-S6 protein in another section from the same block; (B) (case 12, also Figure 4), renal tumour edge (above), stained for p-S6, contrasting with unstained stretched kidney cortex with distorted glomerulus (below); (C) (case 3), carcinoma, intensely stained for p-S6 into regions of kidney sectioned through the papilla (top right); (D) (case 1), lung tissue, from rat with renal carcinoma, showing scattered intensely-stained elements, more clearly seen in magnified region and attributed to metastatic fragments from primary renal tumour.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475221&req=5

toxins-04-00643-f002: Recognition of OTA carcinogenicity in rats. (A) (case 17), H & E stained section of small in situ renal carcinoma (left), matched with position (magnified) of tumour edge elements stained intensely for p-S6 protein in another section from the same block; (B) (case 12, also Figure 4), renal tumour edge (above), stained for p-S6, contrasting with unstained stretched kidney cortex with distorted glomerulus (below); (C) (case 3), carcinoma, intensely stained for p-S6 into regions of kidney sectioned through the papilla (top right); (D) (case 1), lung tissue, from rat with renal carcinoma, showing scattered intensely-stained elements, more clearly seen in magnified region and attributed to metastatic fragments from primary renal tumour.
Mentions: The following descriptions of immunohistochemical findings in tissues are best read in conjunction with rat case context detail and literature cross-referencing tabulated in Supplementary Data. Findings are also summarised in Table 1 and illustrated in Figure 1, Figure 2, Figure 3, Figure 4.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Breakthrough Breast Cancer Research Unit, Guy's Hospital, King's Health Partners AHSC, King's College London School of Medicine, London SE1 9RT, UK. patrycja.gazinska@kcl.ac.uk

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.

Show MeSH
Related in: MedlinePlus