• 1
    Inoue K, Shibutani M, Masutomi N et al. A 13-week subchronic toxicity study of madder color in F344 rats. Food Chem Toxicol 2008; 46: 24152.
  • 2
    Inoue K, Shibutani M, Masutomi N et al. One-year chronic toxicity of madder color in F344 rats – induction of preneoplastic/neoplastic lesions in the kidney and liver. Food Chem Toxicol 2008; 46: 330310.
  • 3
    Inoue K, Yoshida M, Takahashi M et al. Induction of kidney and liver cancers by the natural food additive madder color in a two-year rat carcinogenicity study. Food Chem Toxicol 2009; 47: 18491.
  • 4
    Hachiya N, Takizawa Y, Kawamura T et al. A review of acute toxicity and genotoxicity data on natural food additives (in Japanese). Toxicol Forum 1985; 8: 91105.
  • 5
    Asanoma M, Miyabe M, Sakabe Y. Mutagenicity of natural food additives in Salmonella typhimurium. Report no. II (in Japanese). Ann Rep Nagoya City Public Health Res Inst 1984; 30: 537.
  • 6
    Brown JP, Dietrich PS. Mutagenicity of anthraquinone and benzanthrone derivatives in the Salmonella/microsome test: activation of anthraquinone glycosides by enzymic extracts of rat cecal bacteria. Mutat Res 1979; 66: 924.
  • 7
    Blömeke B, Poginsky B, Schmutte C, Marquardt H, Westendorf J. Formation of genotoxic metabolites from anthraquinone glycosides, present in Rubia tinctorum L. Mutat Res 1992; 265: 26372.
  • 8
    Kawasaki Y, Goda Y, Yoshihira K. The mutagenic constituents of Rubia tinctorum. Chem Pharm Bull 1992; 40: 15049.
  • 9
    Yasui Y, Takeda N. Identification of a mutagenic substance, in Rubia tinctorum L. (madder) root, as lucidin. Mutat Res 1983; 121: 18590.
  • 10
    Westendorf J, Poginsky B, Marquardt H, Groth G, Marquardt H. The genotoxicity of lucidin, a natural component of Rubia tinctorum L. and lucidinethylether, a component of ethanolic Rubia extracts. Cell Biol Toxicol 1988; 4: 22539.
  • 11
    Westendorf J, Marquardt H, Poginsky B, Dominiak M, Schmidt J, Marquardt H. Genotoxicity of naturally occurring hydroxyanthraquinones. Mutat Res 1990; 240: 112.
  • 12
    Westendorf J, Pfau W, Schulte A. Carcinogenicity and DNA adduct formation observed in ACI rats after long-term treatment with madder root, Rubia tinctorum L. Carcinogenesis 1998; 19: 21638.
  • 13
    Poginsky B, Westendorf J, Blömeke B et al. Evaluation of DNA-binding activity of hydroxyanthraquinones occurring in Rubia tinctorum L. Carcinogenesis 1991; 12: 126571.
  • 14
    Marec F, Kollarova I, Jegorov A. Mutagenicity of natural anthraquinones from Rubia tinctorum in the Drosophila wing spot test. Planta Med 2001; 67: 12731.
  • 15
    Inoue K, Yoshida M, Takahashi M et al. Possible contribution of rubiadin, a metabolite of madder color, to renal carcinogenesis in rats. Food Chem Toxicol 2009; 47: 7529.
  • 16
    Jager I, Hafner C, Welsch C, Schneider K, Iznaguen H, Westendorf J. The mutagenic potential of madder root in dyeing processes in the textile industry. Mutat Res 2006; 605: 229.
  • 17
    Ito N, Hasegawa R, Imaida K, Hirose M, Shirai T. Medium-term-liver and multiorgan carcinogenesis bioassays for carcinogens and chemopriventive agents. Exp Toxicol Pathol 1996; 48: 1139.
  • 18
    Dietrich DR, Swenberg JA. Preneoplastic lesions in rodent kidney induced spontaneously or by non-genotoxic agents: predictive nature and comparison to lesions induced by genotoxic carcinogens. Mutat Res 1991; 248: 23960.
  • 19
    Imaida K, Tatematsu M, Kato T, Tsuda H, Ito N. Advantages and limitations of stereological estimation of placental glutathione S-transferase-positive rat liver cell foci by computerized three-dimensional reconstruction. Jpn J Cancer Res 1989; 80: 32630.
  • 20
    Yokohira M, Yamakawa K, Hosokawa K et al. Promotion potential of madder color in a medium-term multi-organ carcinogenesis bioassay model in F344 rats. J Food Sci 2008; 73: T2632.
  • 21
    Tripathi YB, Sharma M, Manickam M. Rubiadin, a new antioxidant from Rubia cordifolia. Indian J Biochem Biophys 1997; 34: 3026.
  • 22
    Rao GM, Rao CV, Pushpangadan P, Shirwaikar A. Hepatoprotective effects of rubiadin, a major constituent of Rubia cordifolia Linn. J Ethnopharmacol 2006; 103: 48490.
  • 23
    Bird RP. Role of aberrant crypt foci in understanding the pathogenesis of colon cancer. Cancer Lett 1995; 93: 5571.
  • 24
    Roncucci L, Stamp D, Medline A, Cullen JB, Bruce WR. Identification and quantification of aberrant crypt foci and microadenomas in the human colon. Human Pathol 1991; 22: 28794.
  • 25
    Pretlow TP, Barrow BJ, Ashton WS et al. Aberrant crypts: putative preneoplastic foci in human colonic mucosa. Cancer Res 1991; 51: 15647.
  • 26
    Yamada Y, Yoshimi N, Hirose Y et al. Sequential analysis of morphological and biological properties of beta-catenin-accumulated crypts, provable premalignant lesions independent of aberrant crypt foci in rat colon carcinogenesis. Cancer Res 2001; 61: 18748.
  • 27
    Hata K, Yamada Y, Kuno T et al. Tumor formation is correlated with expression of ß-catenin-accumulated crypts in azoxymethane-induced colon carcinogenesis in mice. Cancer Sci 2004; 95: 31620.
  • 28
    Hirose Y, Kuno T, Yamada Y et al. Azoxymethane-induced beta-catenin-accumulated crypts in colonic mucosa of rodents as an intermediate biomarker for colon carcinogenesis. Carcinogenesis 2003; 24: 10711.