Pathological outcomes in kidney and brain in male Fischer rats given dietary ochratoxin A, commencing at one year of age

• Published in: Toxins Vol. 2; no. 5; pp. 1100 - 1110
• Main Authors: Mantle, Peter G, Nolan, Christopher C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.05.2010; MDPI
• Subjects: adenoma; Animals; Aspergillus ochraceus - metabolism; Brain - drug effects; Brain - pathology; Carcinogens - toxicity; carcinoma; Carcinoma, Renal Cell - chemically induced; Carcinoma, Renal Cell - pathology; Diet; DNA Damage - drug effects; Dose-Response Relationship, Drug; Kidney - drug effects; Kidney - pathology; Kidney Neoplasms - chemically induced; Kidney Neoplasms - classification; Kidney Neoplasms - pathology; latency; leukemia; Male; neurotoxicity; Ochratoxins - blood; Ochratoxins - toxicity; perfuse-fixed brain histology; Rats; Rats, Inbred F344; renal tumor pathology; Urinalysis; renal tumor pathology; leukemia; adenoma; neurotoxicity; perfuse-fixed brain histology; carcinoma; latency
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins2051100

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.