Carcinogenic potential of alizarin and rubiadin, components of madder color, in a rat medium-term multi-organ bioassay.
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.
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. kenjiabe@nih.go.jp
Kaoru
K
Inoue
Midori
M
Yoshida
Miwa
M
Takahashi
Hitoshi
H
Fujimoto
Makoto
M
Shibutani
Masao
M
Hirose
Akiyoshi
A
Nishikawa
D000818:Animals; D000880:Anthraquinones / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced*; D007680:Kidney Neoplasms / Q000139:chemically induced*; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D010936:Plant Extracts / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D045470:Rubia
D000880:Anthraquinones; D010936:Plant Extracts; C438508:madder color; C010078:alizarin; C072500:rubiadin