STUDIES OF THE CARCINOGENICITY AND MUTAGENICITY OF OCHRATOXIN A. (VOLUMES I AND II) (MYCOTOXIN, MOUSE, NEOPLASIA)

ALISON MORTON BENDELE, Purdue University

Abstract

Ochratoxin A (OA) was evaluated for the induction of bacterial and mammalian cell mutations and for carcinogenicity by 24-month feeding study in male and female B6C3F(,1) mice. The Ames Salmonella assay, using five strains of Salmonella typhimurium histidine auxotrophs, and the gradient plate assay, using eight Salmonella typhimurium histidine auxotrophs and two Escherichia coli tryptophan auxotrophs, were negative with and without metabolic activation using S9 from Aroclor 1254-induced rats for induction of bacterial mutation at concentrations of 50-600 (mu)g OA/plate and 0.1-1000 (mu)g OA/ml, respectively. Unscheduled DNA synthesis in primary cultures of rat hepatocytes was studied in cells exposed to concentrations of OA ranging from 500 (mu)g/ml to 0.000025 (mu)g/ml. No induction of DNA repair synthesis was evident. Induction of forward mutation at the thymidine kinase locus of L5178Y TK+/- mouse lymphoma cells was tested using OA at concentrations ranging from 12.5-0.1 (mu)g/ml with and without S9 from Aroclor 1254-induced rats. OA did not increase the numbers of L5178Y TK-/- mutants over those seen in negative control cultures. Sister chromatid exchanges (SCE) (in vitro) in bone marrow cells of male Chinese hamsters were determined using doses of 25-400 mg OA/kg body weight. No significant increase in SCEs over that seen in controls was found. In a 24-month bioassay, 50 male and 50 female B6C3F(,1) mice per dose group were fed 0, 1, or 40 ppm OA. Renal neoplasms, both carcinomas and adenomas, were increased in male mice of the 40 ppm dose group. Fourteen of 49 animals surviving for at least 20 months had renal carcinomas. Renal adenomas were present in 26 mice, some mice with carcinoma and in other males. Only mice of the 40 ppm dose groups had nephropathy: renal tubular dilatation, attenuation or hyperplasia of lining epithelium, and proliferation of regenerative tubules. The incidence of hepatocellular neoplasms was slightly increased in male and female mice fed OA-containing diets. These studies indicate that OA is not mutagenic for bacteria or mammalian cells under the reported test conditions, but the mycotoxin is a renal carcinogen for male B6C3F(,1) mice, and a weak hepatic carcinogen for both male and female mice of this strain.

Degree

Ph.D.

Subject Area

Animal diseases

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