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

Abstract

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.

Rat Tumour Histopathology Associated with Experimental Chronic Dietary Exposure to Ochratoxin A in Prediction of the Mycotoxin’s Risk for Human Cancers

“…There was also insistence that experimental creation of OTA/DNA adducts in testes of newborn mice, from the mother’s intrauterine exposure to a quite large OTA insult (2.5 mg/kg b wt) about 4 days previously, without discounting OTA/DNA adducts in newborn blood. Application of immunohistochemistry to histology review of rat testis tumours has since showed [ 25 ] the distinctive difference between the natural rat Leydig cell tumours and the germinal cell preponderance of human testicular tumours.…”

Histopathological review of renal pelvic tumours of Balkan nephropathy cases from Southern Serbia

“…From the nearly 60 years of history above it could be expected that most of the renal pelvis tumours sourced for the present study in the context of BEN could be linked aetiologically to that renal disease, but not necessary all. We have recent experience in applying clinical immunohistochemistry (IHC) to review of experimental cancers in rats given protracted or lifetime exposure to ochratoxin A [12,13]. Refinement of histopathology, of value in offering new understanding of the origin and context of cancers, contrasts with literature illustration of BEN-associated tumours [14,15] partly due to risks of postmortem tissue changes in subjects who most likely die at home.…”