title: Possible contribution of rubiadin, a metabolite of madder color, to renal carcinogenesis in rats.
abstract: Madder color (MC) has been shown to exert carcinogenic potential in the rat kidney in association with degeneration, karyomegaly, increased cell proliferation of renal tubule cells and increased renal 8-OHdG levels. To clarify the causal relationship of components and metabolites of MC to renal carcinogenesis, male F344 rats were fed lucidin-3-O-primeveroside (LuP) or alizarin (Alz), and the genotoxic LuP metabolites lucidin (Luc) or rubiadin (Rub) for up to 26 weeks. After one week and four weeks, Luc did not induce any renal changes. In contrast, after one week, cortical tubule degeneration was apparent in the Alz and LuP groups, and cytoplasmic swelling with basophilic change and karyomegaly in the outer medulla was observed only in the Rub group. LuP and Rub increased the proliferative activity of tubule cells in the outer medulla, and Alz and LuP increased renal 8-OHdG levels. After 26 weeks, Rub but not Alz induced atypical tubules, a putative preneoplastic lesion, and karyomegaly in the outer medulla. These results indicate that Rub may be a potent carcinogenic metabolite of MC, targeting proximal tubule cells in the outer medulla, although oxidative stress increased by Alz or LuP might also be involved in renal carcinogenesis by MC.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. k-inoue@nihs.go.jp
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Kuniyoshi
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakashima
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000880:Anthraquinones / Q000633:toxicity*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000378:metabolism / Q000633:toxicity*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D045470:Rubia / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000880:Anthraquinones; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; C438508:madder color; D000080242:8-Hydroxy-2'-Deoxyguanosine; C072500:rubiadin; D003849:Deoxyguanosine