Chronic Administration of the Mutagenic Heterocyclic Amine 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine Induces Cardiac Damage with Characteristic Mitochondrial Changes in Fischer Rats
Fischer-344 rats of both sexes were administered the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) for 52 wk at the dietary level of 400 ppm. Light microscopic and ultrastructural investigation of the myocardium revealed prominent changes in all PhIP-treated male and female animals investigated. These were characterized by a diffuse proliferation of markedly enlarged mitochondria, with abundant cristae and often containing lamellar bodies as inclusions. PhIP is well known to cause DNA adducts in the rat heart, and there are numerous reports of mutations in mitochondrial DNA in both humans and experimental animals being associated with very similar lesions to those observed in the present study. The results thus suggest that this heterocyclic amine induces cardiac damage by the same mechanism.
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