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Immunohistochemical Review of Leydig Cell Lesions in Ochratoxin A-Treated Fischer Rats and Controls

by Diana Herman 1 and Peter Mantle 2,*
1
Pathology Department, County Hospital Timisoara, Timisoara 300736, Romania
2
Centre for Environmental Policy, Imperial College London, South Kensington, London SW7 2AZ, UK
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(8), 480; https://doi.org/10.3390/toxins11080480
Received: 4 July 2019 / Revised: 22 July 2019 / Accepted: 12 August 2019 / Published: 20 August 2019
(This article belongs to the Special Issue Ochratoxin in Food Safety and Public Health)
Ochratoxin A is best known as a potent renal carcinogen in male rats and mice after necessarily protracted ingestion, although valid extrapolation to any human disease has not been verified. The hypothesis that the toxin is a cause of human testicular cancer was proposed a decade ago and has proliferated since, partly through incomplete study of the scientific literature. Archived tumorous rat testes were available from Fischer F344 rats exposed to continuous dietary exposure for half of or the whole life in London in the 2000s. Renal cancer occurred in some of these cases and testicular tumours were observed frequently, as expected, in both treated and untreated animals. Application of clinical immunohistochemistry has for the first time consistently diagnosed the testicular hypertrophy in toxin-treated rats as Leydig cell tumours. Comparison is made with similar analysis of tumorous testes from control (untreated) rats from U.S. National Toxicology Program studies, both of ochratoxin A (1989) and the more recent one on Ginkgo biloba. All have been found to have identical pathology as being of sex cord-stromal origin. Such are rare in humans, most being of germinal cell origin. The absence of experimental evidence of any specific rat testicular cellular pathology attributable to long-term dietary ochratoxin A exposure discredits any experimental animal evidence of testicular tumorigenicity. Thus, no epidemiological connection between ochratoxin A and the incidence of human testicular cancer can be justified scientifically. View Full-Text
Keywords: Leydig cell tumour; testicular cancer; ochratoxin A; immunohistochemistry; F344 rat; evidence-based diagnosis Leydig cell tumour; testicular cancer; ochratoxin A; immunohistochemistry; F344 rat; evidence-based diagnosis
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Herman, D.; Mantle, P. Immunohistochemical Review of Leydig Cell Lesions in Ochratoxin A-Treated Fischer Rats and Controls. Toxins 2019, 11, 480.

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