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Pathological Outcomes in Kidney and Brain in Male Fischer Rats Given Dietary Ochratoxin A, Commencing at One Year of Age

1
Centre for Environmental Policy, Imperial College London, London, SW7 2AZ, UK
2
MRC Applied Neuroscience Group, School of Biomedical Sciences, Queen's Medical Centre, Nottingham, NG7 2UH, UK
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Author to whom correspondence should be addressed.
Toxins 2010, 2(5), 1100-1110; https://doi.org/10.3390/toxins2051100
Received: 9 April 2010 / Revised: 27 April 2010 / Accepted: 11 May 2010 / Published: 13 May 2010
(This article belongs to the Special Issue Ochratoxins)
Malignant renal carcinoma, manifest in morbid ageing rats, is the striking component of an otherwise silent response after about nine months of exposure to ochratoxin A in the first year of life (daily intake ~100–250 µg/kg body weight). Reasons for the long latency are unclear, as is whether there would be a similar carcinogenic response if toxin exposure started at one year of age. Therefore, 24 male Fischer rats were given 100 µg ochratoxin A as a daily dietary contaminant for 35 weeks from age 50 weeks. Plasma ochratoxin A concentration reached a maximum value of ~8 µg/mL within one month of starting the toxin regimen. No renal carcinomas occurred. Four renal adenomas, two of which were only microscopic, were found among the six rats surviving for 110 weeks. The findings raise new questions about a difference between young adults and mature adults in sensitivity of male rats to the ochratoxin A-induced DNA damage necessary for renal carcinogenesis. A pilot histological study of perfuse-fixed brains of the toxin-treated rats showed no gross abnormalities, correlating with the consistent absence of behavioral or neurological disorders from chronic ochratoxin A exposure regimens in the range 100–250 µg/kg/day during the second half of life. Reasoned questioning concerning ochratoxin A as a neurotoxic mycotoxin is made. View Full-Text
Keywords: adenoma; carcinoma; leukemia; renal tumor pathology; latency; neurotoxicity; perfuse-fixed brain histology adenoma; carcinoma; leukemia; renal tumor pathology; latency; neurotoxicity; perfuse-fixed brain histology
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MDPI and ACS Style

Mantle, P.G.; Nolan, C.C. Pathological Outcomes in Kidney and Brain in Male Fischer Rats Given Dietary Ochratoxin A, Commencing at One Year of Age. Toxins 2010, 2, 1100-1110.

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