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 agai nst kidney stones. Recently we reported that lucidin, a hydroxyanthraquinon e 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 carc inogenicity of madder root, three groups of male and female ACI rats receiv ed either a normal diet or a diet supplemented with 1 or 10% drug for a tot al period of 780 days. Weight gain and morbidity were not different among t he three groups. Non-neoplastic lesions related to the treatment were evide nt in the liver and kidneys of both sexes. Moreover, dose-dependent increas es in benign and malignant tumour formation were observed in the liver and kidneys of treated animals. P-32-post-labelling analysis showed an increase in the overall level of DNA adducts observed in the liver, kidney and colo n of rats treated with 10% madder root in the diet for 2 weeks. HPLC analys is of P-32-labelled DNA adducts revealed a peak co-migrating with an adduct obtained after in vitro treatment of deoxyguanosine-3'-phosphate with luci din, These observations suggest that the use of madder root for medicinal p urposes is associated with a carcinogenic risk.