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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.

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  • Authors+Show Affiliations

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    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.

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    Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.

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    Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.

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    Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.

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    Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.

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    Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.

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    Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.

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    Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, 545-8585 Osaka, Japan.

    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.

    Source

    MeSH

    Animals
    Apoptosis
    Butylhydroxybutylnitrosamine
    Carcinogens
    Carcinoma
    Cell Proliferation
    Cocarcinogenesis
    Dietary Supplements
    Dose-Response Relationship, Drug
    Ethanol
    Gene Expression Regulation
    Gene Expression Regulation, Neoplastic
    Male
    Plant Extracts
    Precancerous Conditions
    Propolis
    Random Allocation
    Rats, Inbred F344
    Rats, Mutant Strains
    Solvents
    Urinary Bladder
    Urinary Bladder Neoplasms

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26111810