title: Chemopreventive effects of silymarin against 1,2-dimethylhydrazine plus dextran sodium sulfate-induced inflammation-associated carcinogenicity and genotoxicity in the colon of gpt delta rats.
abstract: Silymarin, a natural flavonoid from the seeds of milk thistle, is used for chemoprevention against various cancers in clinical settings and in experimental models. To examine the chemopreventive mechanisms of silymarin against colon cancer, we investigated suppressive effects of silymarin against carcinogenicity and genotoxicity induced by 1,2-dimethylhydrazine (DMH) plus dextran sodium sulfate (DSS) in the colon of F344 gpt delta transgenic rats. Male gpt delta rats were given a single subcutaneous injection of 40 mg/kg DMH and followed by 1.5% DSS in drinking water for a week. They were fed diets containing silymarin for 4 weeks, starting 1 week before DMH injection and samples were collected at 4, 20 and 32 weeks after the DMH treatment. Silymarin at doses of 100 and 500 p.p.m. suppressed the tumor formation in a dose-dependent manner and the reduction was statistically significant. In the mutation assays, DMH plus DSS enhanced the gpt mutant frequency (MF) in the colon, and the silymarin treatments reduced the MFs by 20%. Silymarin also reduced the genotoxicity of DMH in a dose-dependent manner in bacterial mutation assay with Salmonella typhimurium YG7108, a sensitive strain to alkylating agents, and the maximum reduction was >80%. These results suggest that silymarin is chemopreventive against DMH/DSS-induced inflammation-associated colon carcinogenesis and silymarin might act as an antigenotoxic agent, in part.
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Toyoda-Hokaiwado
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yasui
authors.forename: Mina
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Kenichi
authors.initials: K
authors.lastname: Masumura
authors.forename: Makiko
authors.initials: M
authors.lastname: Takamune
authors.forename: Masami
authors.initials: M
authors.lastname: Yamada
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohta
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takehiko
authors.initials: T
authors.lastname: Nohmi
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002273:Carcinogens / Q000633:toxicity; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D004249:DNA Damage; D016264:Dextran Sulfate / Q000633:toxicity*; D007249:Inflammation / Q000209:etiology*; D008297:Male; D009154:Mutation / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D012838:Silymarin / Q000627:therapeutic use*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000502:physiology*
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D012838:Silymarin; D016264:Dextran Sulfate; D017855:Transferases (Other Substituted Phosphate Groups); C106504:UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase; D019813:1,2-Dimethylhydrazine