A medium-term multi-organ
carcinogenesis bioassay in rats was conducted to assess any possible
tumor promoting effects of
madder color extracted from the root of madder. Male F344 rats were divided into 5 groups of 20 each. All rats of groups 1 to 4 were given DMD treatment, consisted of multicarcinogens,
N-nitrosodiethylamine (DEN),
N-methyl-N-nitrosourea (MNU), and N-bis (2-hydroxypropyl)
nitrosamine (
DHPN), for 4 wk, while group 5 served as untreated control without
carcinogens. The animals were then administered a basal diet containing
madder color at doses of 5.0% (group 1), 2.5% (group 2 with 0.75% additional
dextrin), or 0 (groups 3 with 1.5% additional
dextrin, 4 without
dextrin and 5) for the following 28 wk (total 32 wk). The total amount of
dextrin in groups 1 to 3 diets was adjusted to 1.5% by extra
dextrin because
madder color powder contained
dextrin. Key organs were observed histopathologically and
glutathione S-transferase placental form (GST-P) positive foci of the liver were quantified. In the liver, 5.0% and 2.5% treated groups showed statistically significant dose-related increases in both number and area of GST-P positive foci, number: 2.81 +/- 0.90 and 1.96 +/- 0.93 (groups 1 and 2), area: 0.99 +/- 2.49 and 0.37 +/- 0.77, as compared with control, number: 0.87 +/- 0.72, area: 0.06 +/- 0.06 (group 3). In the kidneys, incidences (and numbers) of
adenoma treated with 5.0% and 2.5%, 47.4% (0.20 +/- 0.24), and 47.4% (0.13 +/- 0.15) (groups 1 and 2) were significantly increased compared to control, 0% (0) (group 3). In conclusion,
madder color demonstrated significant
tumor promoting effects in the liver and kidneys in the DMD model.