INDUCTION OF HEPATIC NODULES IN THE RAT BY ARISTOLOCHIC ACID

Aristolochic acid (AA), used as an anti-inflammatory agent in the past , is known to be mutagenic and carcinogenic to several organs of the r at, including forestomach, renal pelvis and urinary bladder. However, despite the induction of DNA adducts in the liver, no carcinogenic pot ential of AA has been reported in the latter organ. The present study was based on the rationale that the lack of carcinogenicity of AA to t he liver could be because this chemical may not be necrogenic at the d oses examined and liver cell proliferation has been established as an essential component for initiation of liver carcinogenesis in the rat. The results indicated that AA is non-necrogenic to the rat liver. How ever, a single non-necrogenic dose of AA (10 mg/kg b.w., i.p.) given 1 8 hours after 2/3 partial hepatectomy initiated liver cell carcinogene sis. The initiated cells are promotable with 1% dietary orotic acid, a liver tumor promoter, to form glutathione-S-transferase 7-7 positive hepatic foci and nodules.