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β-Glucan extracted from the medicinal mushroom Agaricus blazei prevents the genotoxic effects of benzo[a]pyrene in the human hepatoma cell line HepG2

  • Genotoxicity and Carcinogenicity
  • Published:
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Abstract

The mushroom Agaricus blazei is studied for its nutraceutical potential and as a medicinal supplement. The aim of the present study was to investigate the chemoprotective effect of β-glucan extracted from the mushroom A. blazei against DNA damage induced by benzo[a]pyrene (B[a]P), using the comet assay (genotoxicity) and micronucleus assay with cytokinesis block (mutagenicity) in a human hepatoma cell line (HepG2). To elucidate the possible β-glucan mechanism of action, desmutagenesis or bioantimutagenesis types, three treatment protocols were tested: simultaneous, pre-treatment, and presimultaneous. The results showed that β-glucan does not exert genotoxic or mutagenic effect, but that it does protect against DNA damage caused by B[a]P in every protocol tested. The data suggest that β-glucan acts through binding to B[a]P or the capture of free radicals produced during its activation. On the other hand, the pre-treatment results also suggest the possibility that β-glucan modulates cell metabolism.

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References

  • Angeli JPL, Ribeiro LR, Gonzaga MLC, Soares SA, Ricardo MPSN, Tsuboy MS, Stidl R, Knasmuller S, Linhares RE, Mantovani MS (2006) Protective effects of β-glucan extracted from Agaricus brasiliensis against chemically induced DNA damage in human lymphocytes. Cell Biol Toxicol 22:285–291

    Article  PubMed  CAS  Google Scholar 

  • Bellini MF, Angeli JP, Matuo R, Terezan AP, Ribeiro LR, Mantovani MS (2006) Antigenotoxicity of Agaricus blazei mushroom organic and aqueous extracts in chromosomal aberration and cytokinesis block micronucleus assays in CHO-k1 and HTC cells. Toxicol In Vitro 20:355–360

    Article  PubMed  CAS  Google Scholar 

  • Briede JJ, Godschalk RW, Emans MT, De Kok TM, Van Maanen J, Van Schooten FJ, Kleinjans JC (2004) In vitro and in vivo studies on oxygen free radical and DNA adduct formation in rat lung and liver during benzo[a]pyrene metabolism. Free Radic Res 38:995–1002

    Article  PubMed  CAS  Google Scholar 

  • Chovartovicova D, Machova E, Sandula J, Kogan G (1999) Protective effect of the yeast glucomannan against cyclophosphamide-induced mutagenicity. Mutat Res 444:117–122

    Google Scholar 

  • Darroudi F, Natarajan AT (1991) Use of human hepatoma cells for in vitro metabolic activation of chemical mutagens/carcinogens. Mutagenesis 6:339–403

    Google Scholar 

  • Eastmond DA, Tucker JD (1989) Kinetochore localization in micronucleated cytokinesis-blocked Chinese hamster ovary cells: a new and rapid assay for identifying aneuploidy-inducing agents. Mutat Res 224:517–525

    Article  PubMed  CAS  Google Scholar 

  • Ferguson LR, Roberton AM, Watson ME, Kestell P, Harris PJ (1993) The adsorption of a range of dietary carcinogens by alpha-cellulose, a model insoluble dietary fiber. Mutat Res 319:257–266

    Article  PubMed  CAS  Google Scholar 

  • Ferrari CKB, Torres EAFS (2003) Biochemical pharmacology of functional foods and prevention of chronic diseases of aging. Biomed Pharmacother 57:251–260

    Article  PubMed  CAS  Google Scholar 

  • Fujimiya Y, Suzuki T, Oshiman K, Kobori H, Moriguchu K, Nakashima H, Matumoto Y, Takahara S, Ebina T, Katakura R (1998) Selective tumoricidal effect of soluble proteoglucan exctracted from Basidiomycetes, Agaricus blazei Murill, mediated via natural killer cell activation apoptosis. Cancer Immunol Immunother 46:147–159

    Article  PubMed  CAS  Google Scholar 

  • Gonzaga MLC, Ricardo NMPS, Heatley F, Soares SA (2005) Isolation and characterization of polysaccharides from Agaricus blazei Murill. Carbohydr Polym 60:43–49

    Article  CAS  Google Scholar 

  • Hashimoto T, Nonaka Y, Minato K (2002) Suppressive effect of polysaccharides from the edible and medicinal mushrooms, Lentinus edodes and Agaricus blazei, on the expression of cytochrome P450 s in mice. Biosci Biotechnol Biochem 344:610–614

    Google Scholar 

  • Ito H, Shimura K, Itoh H, Kawadel M (1997) Antitumor effects of a new polysacharide-protein complex (ATOM) prepared from Agaricus blazei (Iwade strain101) Himematsutake” and its mechanisms in tumour-bearing mice. Anticancer Res 17:277–284

    PubMed  CAS  Google Scholar 

  • Kassie F, Rabot S, Uhl W, Huber M, Qin MH, Helma C, Schulte-Hermann R, Knasmuller S (2002) Chemoprotective effects of garden cress (Lepidium sativum) and its constituents towards 2-amino-3-methyl-imidazo[4, 5-f]quinoline (IQ)-induced genotoxic effects and colonic preneoplasic lesions. Carcinogenesis 23:1155–1161

    Article  PubMed  CAS  Google Scholar 

  • Kawagishi H, Katsumi R, Sazawa T, Mizuno T, Hagiwara T, Nakamura T (1988) Citotoxic steroids from the mushroom Agaricus blazei. Phytochemistry 27:2777–2779

    Article  CAS  Google Scholar 

  • Kobayashi H, Sugiyama C, Morikawa Y, Hayashi M, Sofuni T (1995) A comparison between the manual microscopic analysis and computerized image analysis in the single cell gel electrophoresis. MMS Commun 3:103–115

    CAS  Google Scholar 

  • Kobayashi H, Yoshida R, Kanada Y, Fukuda Y, Yagyu T, Inagaki K, Kondo T, Kurita N, Suzuki M, Kanayama N, Terano T (2005) Suppressing effect of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model. J Cancer Res Clin Oncol 131:527–538

    Article  PubMed  CAS  Google Scholar 

  • Krizkova L, Zitnanova I, Mislovicova D, Masarova J, Sasinkova V, Durackova Z, Krajcovica J (2006) Antioxidant and antimutagenic activity of mannan neoglycoconjugates: Mannan–human serum albumine and mannan–penicillin G acylase. Mutat Res 606:72–79

    PubMed  CAS  Google Scholar 

  • Lee BM, Park K-K (2003) Beneficial and adverse effects of chemopreventive agents. Mutat Res 523–524:265–278

    PubMed  Google Scholar 

  • Majer BJ, Hofer E, Cavin C, Lhoste E, Uhl M, Glatt HR, Meinl W, Knasmuller S (2005) Coffee diterpenes prevent the genotoxic effects of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) and N-nitrosodimethylamine in a human derived liver cell line (HepG2). Food Chem Toxicol 43:433–441

    Article  PubMed  CAS  Google Scholar 

  • Mantovani MS, Bellini MF, Angeli JP, Oliveira RJ, Silva AF, Ribeiro LR (2008) beta-Glucans in promoting health: Prevention against mutation and cancer. Mutat Res 658:154–161

    Article  PubMed  CAS  Google Scholar 

  • Mizuno T, Hagiwara T, Nakamura T, Ito H, Shimura K, Sumiya T, Asakura A (1990) Antitumour activity and some properties of water-soluble polysaccharides from “Himematsutake”, the fruiting body of Agaricus blazei Murill. Agric Biol Chem 54:2889–2896

    CAS  Google Scholar 

  • Okamoto T, Kodoi R, Nonaka Y (2004) Lentinan from shiitake mushroom (Lentinus edodes) suppresses expression of cytochrome P450 1A subfamily in the mouse liver. Biofactors 21:407–374

    Article  PubMed  CAS  Google Scholar 

  • Oliveira RJ, Matuo R, Silva AF, Matiazi HJ, Mantovani MS, Ribeiro LR (2007) Protective effect of β-glucan extracted from Saccharomyces cerevisiae, against DNA damage and cytotoxicity in wild-type (K1) and repair-deficient (xrs5) CHO cells. Toxicol In Vitro 21:41–52

    Article  PubMed  CAS  Google Scholar 

  • Speit G, Hartmann A (2005) The comet assay: a sensitive genotoxicity test for the detection of DNA damage. Methods Mol Biol 291:85–95

    PubMed  CAS  Google Scholar 

  • Takaku T, Kimura T, Okuda H (2001) Isolation of an antitumour compound from Agaricus blazei Murill and its mechanism of action. J Nutr 131:1409–1413

    PubMed  CAS  Google Scholar 

  • Talorete TPN, Isoda H, Maekawa T (2002) Agaricus blazei (class Basidiomycotina) aqueous extract enhances the expression of c-Jun protein in MCF7 cell. J Agric Food Chem 50:5162–5166

    Article  PubMed  CAS  Google Scholar 

  • Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221

    Article  PubMed  CAS  Google Scholar 

  • Uhl M, Helma C, Knasmuller S (1999) Single cell gel electrophoresis assay with human-derived hepatoma (HepG2) cells. Mutat Res 441:215–224

    PubMed  CAS  Google Scholar 

  • Uhl M, Helma C, Knasmuller S (2000) Evaluation of the single cell gel electrophoresis assay with human hepatoma (HepG2) cells. Mutat Res 468:213–225

    PubMed  CAS  Google Scholar 

  • Walter-Sack I, Klotz U (1996) Influence of diet and nutritional status on drug metabolism. Clin Pharmacokinet 31:47–64

    Article  PubMed  CAS  Google Scholar 

  • Williams GM, Williams CM, Weisburger JH (1999) Diet and cancer prevention: the fiber first diet. Toxicol Sci 52:72–86

    PubMed  CAS  Google Scholar 

  • Yoshioka Y, Tabeta R, Saito H, Uehara N, Fukuoka F (1985) Antitumor polysaccharide from P. ostreatus (FR.) QUÉL.: isolation and structure of a b-glucan. Carbohydr Res 140:93–100

    Article  PubMed  CAS  Google Scholar 

  • Zekovic DB, Kwiatkowski S, Vrvic MM, Jakovljevic D, Moran CA (2005) Natural and modified (1 → 3)-β-D-Glucans in health promotion and disease alleviation. Crit Rev Biotechnol 25:205–230

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank FAEPE/UEL, CNPq, and CAPES for financial support and grants. We also thank Prof. Sandra S. Soares for donating the samples of β-glucan. We are grateful to Dr A. Leyva for English editing of the manuscript.

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Correspondence to Mário Sérgio Mantovani.

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Angeli, J.P.F., Ribeiro, L.R., Bellini, M.F. et al. β-Glucan extracted from the medicinal mushroom Agaricus blazei prevents the genotoxic effects of benzo[a]pyrene in the human hepatoma cell line HepG2. Arch Toxicol 83, 81–86 (2009). https://doi.org/10.1007/s00204-008-0319-5

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  • DOI: https://doi.org/10.1007/s00204-008-0319-5

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