ABSTRACT
The chemopreventive potential of an Agaricus blazei (Ab) Murrill mushroom meal was investigated in a medium-term rat liver carcinogenesis assay. Male Wistar rats initiated for hepatocarcinogenesis with diethylnitrosamine (DEN, 200 mg/kg i.p.) were fed during a 6-week period with the dry powdered mushroom strains Ab 29 or 26, each one with opened (OB) or closed basidiocarp (CB), mixed at 10% level in a basal diet. All experimental animals and controls were subjected to partial hepatectomy at week 3 and killed at week 8. Chemopreventive activity of the mushroom meal was observed for the Ab 29 (OB and CB) and Ab 26 (CB) strains in terms of the number of putative preneoplastic altered foci of hepatocytes which express either the enzyme glutathione S-transferase, placental form (GST-P+) or the transforming growth factor-alpha, and for the Ab 29 (OB) and Ab 26 (CB) strains on the size of GST-P+ foci. This was associated with inhibition of foci cell proliferation in the animals fed the Ab 29 (OB) and Ab 26 (CB) strains. The results suggest that the protective influence of the Ab meal against the DEN potential for rat liver carcinogenicity depends on both the strain and period of mushroom harvest.
Subject(s)
Agaricus/chemistry , Anticarcinogenic Agents/pharmacology , Liver Neoplasms, Experimental/prevention & control , Precancerous Conditions/prevention & control , Animals , Anticarcinogenic Agents/chemistry , Body Weight/drug effects , Carcinogens/antagonists & inhibitors , Carcinogens/toxicity , Diet , Diethylnitrosamine/antagonists & inhibitors , Diethylnitrosamine/toxicity , Eating , Glutathione Peroxidase/metabolism , Immunohistochemistry , Liver/drug effects , Liver/enzymology , Liver/pathology , Liver Neoplasms, Experimental/chemically induced , Male , Organ Size/drug effects , Precancerous Conditions/chemically induced , Proliferating Cell Nuclear Antigen/metabolism , Rats , Rats, Wistar , Transforming Growth Factor alpha/metabolism , Weight Gain/drug effectsABSTRACT
Agaricus blazei Murill is a medicinal mushroom native to Brazil. The present work assessed the clastogenic and anticlastogenic potential of organic extracts (ethanol and chloroform/methanol) from the lineage AB97/11 in chinese hamster CHO-K(1) (wild type) and CHO-xrs5 (repair deficient) cells using the chromosome aberration (CA) and sister chromatid exchange (SCE) assays. In these experimental conditions were observed: (a) anticlastogenic effect at concentrations of 0.06 and 0.09% of the EtOH extract and at the 0.03 and 0.06% concentrations of the C/MetOH extract in CHO-K(1); (b) absence of protector effect on CHO-xrs5 cells; and (c) absence of protector effect in the SCE assay. These results indicate that organic extracts of A. blazei lineage AB97/11 present bio-antimutagenic type protective activity.
Subject(s)
Agaricus/chemistry , Antimutagenic Agents/pharmacology , Chromosome Aberrations , Plant Extracts/pharmacology , Sister Chromatid Exchange , Animals , CHO Cells , Cricetinae , Mutagenicity Tests , Plants, MedicinalABSTRACT
This study was performed to evaluate the efficiency of four different lineages (95/01, L1, 96/22 and JABK) of Lentinula edodes (BERK.) Pegler mushroom (shiitake) for inhibiting the N-ethyl-N-nitrosourea (ENU) clastogenicity in vivo. Male Swiss mice (10 animals/group) were treated during 15 consecutive days with dried mushroom added to basal diet under three different concentrations (1, 5 and 10%). At day 15, mice were intraperitoneally injected with ENU (50 mg/kg body weight) and sacrificed 24 h later for evaluation of micronucleated bone marrow polychromatic erythrocytes (MNPCE). Negative and positive controls (10 animals each), receiving basal diet and saline or ENU ip injection, respectively, were also evaluated. Results showed that pretreatments with diets containing the lineages 95/01, L1 and 96/22 reduce the frequencies of MNPCE induced by ENU. The absence of an antimutagenic activity for the lineage JABK might be related to intrinsic differences among the lineages such as biochemical composition. Taken together, our data show that the differences in protective activities of the mushrooms need to be clarified in further studies and the mechanisms for such activities need to be investigated.
Subject(s)
Antimutagenic Agents/pharmacology , Shiitake Mushrooms/chemistry , Animals , Antimutagenic Agents/isolation & purification , Body Weight/drug effects , Bone Marrow/drug effects , Diet , Dose-Response Relationship, Drug , Eating/drug effects , Erythrocytes/drug effects , Erythrocytes/ultrastructure , Ethylnitrosourea/toxicity , Male , Mice , Micronucleus Tests , Mutagens/toxicity , Phenotype , Shiitake Mushrooms/genetics , Species SpecificityABSTRACT
Agaricus blazei Murrill extracts have previously been shown to have anticarcinogenic and antimutagenic properties. These results suggest that antimutagenic activity, besides the modulation of the immune system, might be involved in the anticarcinogenic action of A. blazei. To investigate the possible antimutagenic effect of A. blazei in vivo, we evaluated its effect on clastogenicity induced by cyclophosphamide (CP) in mice, using the micronucleus test in bone marrow (MNPCE) and in peripheral blood (MNRET). Male Swiss mice were treated with CP (25 or 50mg/kg i.p.) or with CP plus mushroom solution at three different temperatures: 4, 21, and 60 degrees C. Aqueous solution of a mixture from various lineages of the mushroom inhibited induction of micronuclei by CP in bone marrow and in peripheral blood of mice. In contrast to the mixture of lineages, a single isolated lineage did not lead to a reduction of CP-induced MN frequencies in either bone marrow or blood cells of mice. The results suggest that under certain circumstances these mushrooms exhibit antimutagenic activities that might contribute to an anticarcinogenic effect.
Subject(s)
Agaricus/chemistry , Antimutagenic Agents/pharmacology , DNA Damage/drug effects , Plant Extracts/pharmacology , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/pathology , Cyclophosphamide/toxicity , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Mice , Micronucleus Tests , Mutagens/toxicity , Reticulocytes/drug effects , Reticulocytes/pathologyABSTRACT
We evaluated the antimutagenic effect of Letinula edodes (Berk.) Pegler (Shiitake) on the frequency of micronuclei in mice treated with N-ethyl-N-nitrosourea (ENU) or cyclophosphamide (CP). Mice were orally (gavage) pretreated for 15 consecutive days with solutions of Shiitake (0.6 ml per day, gavage) prepared at three different temperatures: 4, 21 (RT), and 60 degrees C. Then, the animals were intraperitoneally injected on day 15 with CP (25 or 50mg/kg) or ENU (50 mg/kg) and killed 24 or 48 h after treatment for evaluation of micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow and micronucleated reticulocytes (MNRETs). A mixture of L. edodes lineages (LE 95/016, 96/14, 96/17, 96/22, 96/23, 97/27, and 97/28) significantly decreased the frequencies of MNPCEs and MNRETs induced by CP (25 and 50mg/kg). When a single lineage from the mixture (LE 96/17) was tested we also found a significant reduction in the frequencies of MNPCEs and MNRETs induced by both CP or ENU (50mg/kg). The comet assay was also performed 3h after ENU treatment using mice pretreated with the single lineage (LE 96/17) of L. edodes. The results showed a high degree of variability with some indications of an antigenotoxic effect. Taken together, our data show that solutions from Shiitake inhibit in vivo mutagenicity of CP and ENU.
