The carcinogenic action of aristolochic acid in rats

Abstract

Male and female Wistar rats treated orally with 0.1, 1.0 or 10.0 mg/kg/day aristolochic acid as its sodium salt (AA) developed a high incidence of tumours dependent on dose and time. After 3 months' treatment 1.0 and 10.0 mg/kg AA led to severe papillomatosis of the forestomach with occasional signs of malignancy. Three to 6 months later without further treatment the rats developed squamous cell carcinomas in the forestomach with formation of metastases. At the same time anaplasia of the tubular epithelium and mainly adenomas appeared in the renal cortex. The transitional epithelium of the renal pelvis and the urinary bladder showed hyperplasia, papillomas or carcinomas. For the low dose (0.1 mg/kg) the treatment with AA varied between 3 and 12 months. No tumours were observed in the first 6 months of the study. After 12 and 16 months, however, papillomas or squamous cell carcinomas also occurred in the forestomach. In addition, hyperplasia of the transitional epithelium of the renal pelvis was found while the renal cortex and the urinary bladder remained normal.