Madder color (MC), a food coloring extracted from roots of Rubia tinctorum L., has been proven to exert carcinogenicity in the rat kidney and liver. Furthermore, it induces
DNA adducts in the kidney, liver, and colon. MC is in fact composed of
anthraquinones such as lucidin-3-O-primeveroside and
alizarin. To clarify which of these might be responsible for the carcinogenicity, a rat medium-term multi-organ
carcinogenesis bioassay was performed focusing on the kidney, liver, and colon. Male 6-week-old F344 rats after receiving five different
carcinogens were fed a diet containing either 0.008% or 0.04% of
alizarin or
rubiadin, a metabolite of lucidin-3-O-primeveroside, for 23 weeks. Treatment with 0.04%
rubiadin significantly increased atypical renal tubules/
hyperplasias and induced renal cell
adenomas and
carcinomas. Renal cell
tumors were also increased with 0.04%
alizarin, although at lower incidence than with
rubiadin. In addition,
glutathione S-transferase placental form-positive liver cell foci and large intestinal dysplasias were significantly increased with 0.04%
rubiadin. These results indicate that both
rubiadin and
alizarin can increase renal preneoplastic lesions, the potential of the latter being weaker.
Rubiadin may also target the liver and large intestine, suggesting a major role in
madder color-induced carcinogenicity.