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Suppression of Arylamine Toxicity in the Fischer-344 Rat Following Ingestion of a Complex Mixture

Department of Physiology, Pharmacology, and Toxicology, Louisiana State University, Baton Rouge, Louisiano 70803

David G. Baker

Department of Veterinary Pathology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, dbaker{at}mail.vetmed.lsu.edu.

H. Wayne Taylor

Department of Veterinary Pathology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803

Steven A. Barker

Department of Physiology, Pharmacology, and Toxicology, Louisiana State University, Baton Rouge, Louisiano 70803

Jay C. Means

Department of Physiology, Pharmacology, and Toxicology, Louisiana State University, Baton Rouge, Louisiano 70803, Department of Chemistry, Western Michigan University, Kalamazoo, Michigan 49008

The toxic effects of a mixture of 2-aminoanthracene (2-AA), benzanthracene (BA), and dinitropyrene isomers (DNP), and the toxic effects of these compounds individually, were investigated in the Fischer-344 rat following dietary exposure via a powdered basal diet. Animals were sacrifi ced at 14-, 30-, and 80-day s of dietary exposure. Exposure to dietary 2-AA alone induced anorexia, cachexia, variable mortality, and altered serum chemistry profi les in the F-344 rat. Reduced lymphocyte counts were also shown in rats exposed to 2-AA. A temporal pattern of effect of 2-AA dietary exposure was observed in the progression of hepatic lesions in exposed animals. Dietary exposure to either DNP isomers or BA at a 10-fold higher concentration in the diet, relative to 2-AA, did not induce detectable toxic responses.

However, exposure of rats to a mixture of 2-AA, BA, and DNP isomers (100 mg/kg, 1.0 g/kg, and 1.0 g/kg of diet, respectively) resulted in the attenuation of toxic effects when compared to exposure of F-344 rats to 2-AA alone. These results indicate that the toxic effects of 2-AA are suppressed by co-administration of DNP and BA and suggest that compound interactions need to be considered when predicting the toxic potential of specifi c environmental pollutants.

Key Words: Polycyclic aromatic hydrocarbon • PAH • dietary

Toxicologic Pathology, Vol. 29, No. 3, 333-343 (2001)
DOI: 10.1080/019262301316905291


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