Carcinogenicity and DNA adduct formation observed in ACI rats after long-term treatment with madder root, Rubia tinctorum L

Madder root, Rubia tinctorum L., is a traditional herbal medicine used against kidney stones. Recently we reported that lucidin, a hydroxyanthraquinone derivative present in this plant, is mutagenic in bacteria and mammalian cells. We also demonstrated the formation of DNA adducts in tissue culture and mice after treatment with this compound. To elucidate the possible carcinogenicity of madder root, three groups of male and female ACI rats received either a normal diet or a diet supplemented with 1 or 10% drug for a total period of 780 days. Weight gain and morbidity were not different among the three groups. Non-neoplastic lesions related to the treatment were evident in the liver and kidneys of both sexes. Moreover, dose-dependent increases in benign and malignant tumour formation were observed in the liver and kidneys of treated Animals. 32P-post-labelling analysis showed an increase in the overall level of DNA adducts observed in the liver, kidney and colon of rats treated with 10% madder root in the diet for 2 weeks. HPLC analysis of 32P-labelled DNA adducts revealed a peak co-migrating with an adduct obtained after in vitro treatment of deoxyguanosine-3'-phosphate with lucidin. These observations suggest that the use of madder root for medicinal purposes is associated with a carcinogenic risk.