title: Ethanol-extracted propolis enhances BBN-initiated urinary bladder carcinogenesis via non-mutagenic mechanisms in rats.
abstract: Ethanol-extracted propolis (EEP) is used for medical, dietetic and cosmetic purposes. In this study, the effects of EEP on urinary bladder carcinogenesis, its underlying mechanism and in vivo genotoxicity were investigated. In experiment 1, rats were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 2 or 4 weeks followed by dietary administration of 0.125, 0.25, 0.5 or 1% EEP for 4 or 32 weeks, respectively. At week 6, the mRNA levels of top2a, cyclin D1 and survivin were significantly elevated in the 0.5 and 1% EEP groups. At week 36, the incidence and multiplicity of urothelial carcinomas and total tumors were markedly elevated in all EEP groups. In experiment 2, rats were fed basal diet or the 1% EEP diet for 13 weeks without carcinogen initiation. Increases in urinary precipitate, cell proliferation and incidence of simple hyperplasia were observed in the 1% EEP group. In experiment 3, dietary administration of 2.5% EEP to gpt delta rats for 13 weeks did not induce any obvious mutagenicity in the urinary bladder urothelium. Taken together, EEP enhanced BBN-initiated rat urinary bladder carcinogenesis in a non-genotoxic manner through increasing formation of urinary precipitate, enhancing cell proliferation and inhibiting apoptosis during the early stages of carcinogenesis.
authors.affiliation: Department of Toxicology, School of Public Health and Tropical Medicine, Southern Medical University, No. 1838 North Guangzhou Road, 510515 Guangzhou, China; Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xie
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Gi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujioka
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Doi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Yamano
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tachibana
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.
authors.forename: He
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Kakehashi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan. Electronic address: wani@med.osaka-cu.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine / Q000737:chemistry / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D002277:Carcinoma / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003043:Cocarcinogenesis / Q000378:metabolism* / Q000473:pathology; D019587:Dietary Supplements / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000737:chemistry; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011429:Propolis / Q000737:chemistry*; D011897:Random Allocation; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains; D012997:Solvents / Q000737:chemistry; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism / Q000473:pathology
chemical_list: D002273:Carcinogens; D010936:Plant Extracts; D012997:Solvents; D002085:Butylhydroxybutylnitrosamine; D000431:Ethanol; D011429:Propolis
keywords: Ethanol-extracted propolis; Mutagenicity; Urinary bladder carcinogenesis; Urinary precipitate