Using the Ames bacterial mutagenicity test, the comet assay, and an in vivo micronucleus test, we investigated the effect of the chemoprotective substance phenethyl isothiocyanate (PEITC) on the mutagenic activity of indirect-acting mutagens and carcinogens aflatoxin B1 (AFB1) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and direct-acting mutagen and carcinogen N-nitroso-N-methylurea (MNU). In the Ames test, the antimutagenic activity of PEITC was studied in the concentration range 0.3–300 µg/plate. PEITC at concentrations of 0.3, 3 and 30 µg/plate reduced dose-dependently mutagenicity of AFB1 and IQ in both S.typhimurium TA98 and TA100 strains. In the case of the direct mutagen MNU, the antimutagenic effect of PEITC was detected only at concentration of 30 µg/plate in the strain TA100. The PEITC concentration 300 µg/plate was toxic in the Ames test. The 24 h pre-treatment of HepG2 cells with PEITC at concentration 0.15 µg/ml resulted in a significant decrease of DNA breaks induced by MNU at concentrations 0.25 and 0.5 mM. Although a trend towards reduced strand break level were determined also at PEITC concentrations 0.035 and 0.07 µg/ml it did not reach the statistical significance. No effect, however, of PEITC on IQ-induced DNA breaks was observed. Chemopreventive effect of PEITC was revealed also in vivo. Pretreatment of mice with PEITC concentrations of 25 and 12.5 mg/kg b.w. administered to mice in three daily doses resulted in reduction of micronucleus formation in mice exposed to all three mutagens under study, with statistically significant effect at concentration of 25 mg/kg. Results of this study indicate that the strong PEITC antimutagenic properties may have an important role in the prevention of carcinogenesis and other chronic degenerative diseases that share some common pathogenetic mechanisms.

• MeSH
• aflatoxin B1 toxicita   MeSH
• antimutagenní látky aplikace a dávkování   farmakologie   MeSH
• chinoliny toxicita   MeSH
• financování organizované MeSH
• isothiokyanatany aplikace a dávkování   farmakologie   MeSH
• karcinogeny toxicita   MeSH
• kultivované buňky MeSH
• lidé MeSH
• methylnitrosomočovina toxicita   MeSH
• mutageny toxicita   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• Salmonella typhimurium MeSH
• testy genotoxicity MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH

We investigated single-strand breaks and endonuclease III-sensitive sites in DNA along with gamma-irradiation-specific DNA-repair activity in hepatocytes and frequencies of micronuclei in polychromatic bone-marrow erythrocytes of male NMRI mice (2 months old, weight 30-35 g) during sub-acute inhalation exposure to 1,3-butadiene (28 days, 500 mg/m3) and up to 28 days after the exposure. Concentrations of 1,3-butadiene in blood, an indicator of internal exposure, moderately increased during the exposure period. The most interesting finding was that gamma-irradiation-specific DNA-repair activity gradually increased during exposure, being significantly higher compared with control levels on days 7 and 28 of exposure (P = 0.005 and 0.035, respectively), reaching a maximum on day 1 after the termination of exposure (P = 0.003) and then returning to control levels. A significant correlation between gamma-irradiation-specific DNA-repair activity and the concentration of 1,3-butadiene in blood (R = 0.866, P = 0.050) supports a possible induction of DNA-repair activity by the exposure to 1,3-butadiene and formation of its metabolites. The initial increase in micronucleus frequency (micronuclei per 1000 cells) in the exposed mice continuously decreased from 20.4 +/- 5.1 (day 3) to 15.1 +/- 3.2 (day 28) within the exposure period, and subsequently from 12.4 +/- 5.1 to 4.6 +/- 1.6 in the period following termination of the 1,3-butadiene exposure, while micronucleus frequencies in control animals were significantly lower (from 1.7 +/- 1.5 to 4.2 +/- 0.8).

• MeSH
• aplikace inhalační MeSH
• buňky kostní dřeně cytologie   MeSH
• butadieny aplikace a dávkování   krev   toxicita   MeSH
• deoxyribonukleasa (pyrimidinový dimer) metabolismus   MeSH
• erytrocyty cytologie   MeSH
• financování organizované MeSH
• hepatocyty metabolismus   MeSH
• kometový test MeSH
• mikrojádra chromozomálně defektní MeSH
• myši MeSH
• oprava DNA MeSH
• poškození DNA MeSH
• proteiny z Escherichia coli metabolismus   MeSH
• regresní analýza MeSH
• záření gama MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH

There is an increasing evidence that dietary phytochemicals may play important roles as chemopreventive or chemotherapeutic agents in prevention of many diseases, including tumors. The purpose of this study was to examine antimutagenic effects and effect on the immune response of representative series of substances which commonly occur in human diet. Using the Ames bacterial mutagenicity test and in vivo chemiluminescence test, we investigated antigenotoxic and immunomodulatory effects of juices and vegetable homogenates (carrot + cauliflower, cauliflower, red cabbage, broccoli, onion, garlic) on the genotoxicity of AFB1 and pyrolysates of aminoacids. Using the Ames test and in vivo micronucleus, the chemiluminescence test, the blastic transformation test and the comet assay we examined antimutagenic effects of chemically identified chemoprotective substances in the pure form (resveratrol, diallylsulphide, phenethyl isothiocyanate, ellagic acid, epigallocatechin gallate, genistein and curcumin) on mutagenicity induced by three reference mutagens: aflatoxin B1 (AFB1), 2-amino-3-metylimidazo[4,5,-f] chinolin (IQ) and N-nitroso- N-metylurea (MNU) and effect of phytochemicals on the immunosuppression caused by these mutagens. All complete vegetable homogenates and substances of plant origin tested, showed a clear antimutagenic and immunomodulatory activities on mutagenicity and immunosuppression induced by reference mutagens. Only in the Ames test the effect of some phytochemicals against direct mutagen MNU was lower compared to indirect mutagens AFB1 and IQ. Similarly, resveratrol and epigallocatechin gallate had no inhibitory effect on mutagenicity MNU in the Ames test.

• MeSH
• aktivace lymfocytů účinky léků   MeSH
• antimutagenní látky * farmakologie   MeSH
• fyziologie výživy * MeSH
• mutace účinky léků   MeSH
• mutageny toxicita   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádory imunologie   prevence a kontrola   MeSH
• testy genotoxicity MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zelenina * imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH

A wide array of antioxidative and anti-inflammatory substances derived from edible plants have been reported to possess chemopreventive and chemoprotective activities. Among the most extensively investigated and well-defined dietary chemopreventives is curcumin. Using the Ames test and in vivo micronucleus test, chemiluminescence test, blastic transformation test, and comet assay, we examined the antimutagenic effects of the chemically identified chemoprotective substance curcumin (diferuloylmethane) in the pure form on mutagenicity induced by three reference mutagens: aflatoxin B1 (AFB1), 2-amino-3-metylimidazo[4,5,-f] chinolin (IQ), and N-nitroso-N-metylurea (MNU), and the effect of curcumin on the immunosuppression caused by these mutagens. Curcumin in the pure form showed a clear antimutagenic and immunomodulatory activities on mutagenicity and immunosuppression induced by reference mutagens.

• MeSH
• aktivace lymfocytů genetika   MeSH
• antimutagenní látky analýza   MeSH
• imunologické techniky metody   MeSH
• kometový test MeSH
• kurkumin * analýza   metabolismus   MeSH
• luminiscenční měření MeSH
• myši MeSH
• Salmonella typhimurium MeSH
• testy karcinogenity * MeSH
• Check Tag
• myši MeSH
• Publikační typ
• práce podpořená grantem MeSH

• Konspekt
• Kuchařství. Potraviny. Vařená jídla

Green tea is the second-most consumed beverage in the world (water is the first one) and has been used medicinally for centuries in India and China. The active substances in the green tea are polyphenols (catechins) and flavonols which possess a potent antioxidant activity. Epigallocatechin gallate (EGCG) is one of the four major green tea catechins. Using the Ames test, micronucleus test, comet assay, chemiluminescence test, and blastic transformation test, we examined the antimutagenic effects of chemoprotective substance epigallocatechin gallate (EGCG) in the pure form on the mutagenicity induced by three reference mutagens: aflatoxin B1 (AFB1), 2-amino-3-methylimidazo [4,5-f] qui-noline (IQ), and N-nitroso-N-methylurea (MNU), and the effect of EGCG on the immunosuppression caused by these mutagens. Using the Ames test the dose dependent antimutagenic activity of EGCG was proved against indirect mutagens AFB1 and IQ, but not against the direct mutagen MNU. In the micronucleus test, EGCG had antimutagenic effect upon all three mutagens. EGCG decreased the level of DNA breaks induced by AFB1 in bone marrow cells and colon epithelium, and the level of DNA breaks induced by MNU in colon cells to the level found in control. The reparatory effect of EGCG on immunosupression induced by all three carcinogenic compounds was proved using chemiluminescence and blastic trasformation tests.

• Klíčová slova
• zelený čaj, epigalokatechin galát,
• MeSH
• aktivace lymfocytů MeSH
• antimutagenní látky * analýza   MeSH
• čaj * chemie   imunologie   MeSH
• katechin * analogy a deriváty   analýza   genetika   MeSH
• kometový test MeSH
• luminiscenční měření MeSH
• myši inbrední BALB C MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• Konspekt
• Průmysl nápojů. Kvasný průmysl. Průmysl pochutin

A great variety of health benefits including the protection against breast and prostate cancers has been attributed to the soya consumption, because of the presence of soy beans isoflavones, genistein, and others. We investigated the antigenotoxic effect of genistein on the genotoxicity of three mutagens and carcinogens – aflatoxine B1 (AFB1), 2-amino-3-methylimidazo [4,5-f]quinoline (IQ), and N-nitroso-N-methylurea (MNU), using the Ames bacterial mutagenicity test and the micronucleus test. In the Ames test on Salmonella typhimurium, a significant antimutagenic effect was determined against the indirect mutagen AFB1 in two strains, TA98 and TA100. However, the effect on the IQ indirect mutagenicity was more pronounced in the test with TA98 than with TA100. The mutagenicity of the direct mutagen MNU was suppressed by genistein only at its highest concentration used (300 µg/plate). The protective effect of genistein against all three mutagens was proved in the micronucleus test as the treatment of mice with the combinations of genistein and mutagens resulted in a significant reduction of the number of micronuclei in comparison with the number of micronuclei induced by the individual mutagens alone.

• Klíčová slova
• chemoprevence, rakovina prsu, rakovina prostaty,
• MeSH
• aflatoxin B1 škodlivé účinky   MeSH
• antimutagenní látky analýza   chemie   MeSH
• chemoprofylaxe MeSH
• flavonoidy farmakokinetika   genetika   MeSH
• fytoestrogeny analýza   MeSH
• genistein * farmakokinetika   škodlivé účinky   MeSH
• mikrojaderné testy MeSH
• modulátory estrogenních receptorů MeSH
• mutageny analýza   MeSH
• myši inbrední BALB C MeSH
• testy genotoxicity MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• Konspekt
• Obecná biologie
• Fyziologie člověka a srovnávací fyziologie

Pomocí Amesova testu a in vivo mikronukleus testu jsme sledovali antigenotoxický efekt kyseliny elagové (EA) na genotoxicitu tří mutagenů: amino-methylimidazo-chinolinu (IQ), aflatoxinu B1 (AFB1) a N-nitroso-N-methylurey (MNU). Kyselina elagová je fenolová sloučenina, přirozeně se vyskytující v různých druzích ovoce a zeleniny. Její efekt na imunosupresivní aktivitu mutagenů jsme rovněž sledovali in vivo chemiluminescenčním testem. V Amesově testu kyselina elagová v koncentracích 300 a 30 μg na misku prokazatelně inhibovala mutagenní aktivitu dvou nepřímých mutagenů IQ a AFB1. Koncentrace 300 μg na misku měla nejsilnější efekt na mutagenitu všech koncentrací IQ v testech na kmeni TA98 Salmonella typhimurium, zatímco na kmeni TA100 byla koncentrace 30 mg na misku efektivnější než koncentrace 300 μg na misku. Také v kombinaci s různými koncentracemi AFB1 se kyselina elagová chovala jako silný antimutagen. V tomto případě však nižší ze dvou účinných koncentrací – 30 μg na misku měla mnohem větší antimutagenní efekt než koncentrace 300 μg na misku na obou kmenech. V kombinaci s přímým mutagenem MNU nevykazovala kyselina elagová významný antimutagenní efekt ve většině koncentrací testovaných na kmeni TA100. Jenom nejvyšší koncentrace kyseliny elagové redukovala mutagenitu MNU slabě, a to pouze v kombinaci se dvěma nižšími koncentracemi MNU. V mikronukleus testu, třídenní p.o. aplikace kyseliny elagové předcházející aplikaci AFB1, IQ nebo MNU významně redukovala počty mikrojader indukované samotnými mutageny v polychromatofilních erytrocytech myší. Chemiluminescenční test na myších granulocytech prokázal, že kyselina elagová nejen zabraňuje inhibičnímu účinku mutagenů na tvorbu volných kyslíkových radikálů a peroxidu vodíku, ale jejich tvorbu v kombinaci s mutageny stimuluje dokonce ve vyšším rozsahu, než je stimulace samotnou kyselinou elagovou. Z těchto výsledků vyvozujeme, že kyselina elagová silně reparuje imunosupresivní efekt testovaných mutagenů.

Using the Ames bacterial mutagenicity test and an in vivo micronucleus test, we investigated the antigenotoxic effect of ellagic acid on the genotoxicity of three mutagens: amino-methylimidazo-quinoline (IQ), aflatoxin B1 (AFB1), and N-nitroso-N-methylurea (MNU). Ellagic acid is a naturally occurring phenolic compound which is found in a variety of soft fruits and vegetables. The effect of this compound on the immunosuppressive activity of mutagens was followed in vivo by the chemiluminescence test. In the Ames assay, ellagic acid at concentrations of 300 and 30 μg/plate demonstrably inhibits the mutagenic activity of two indirect mutagens: IQ and AFB1. The concentration of 300 μg/plate had the strongest effect on mutagenicity of all concentrations of IQ in strain TA98 of Salmonella typhimurium, whereas in strain TA100 concentration of 30 μg per dish of ellagic acid was more effective than 300 μg per plate. Also in combination with different concentrations of AFB1, ellagic acid proved to be a strong antimutagen. In this case the lower of the two effective concentrations – 30 μg/plate – had a much greater antimutagenic effect on both strains tested than 300 μg/plate. In combination with the direct mutagen MNU, ellagic acid did not show any marked antimutagenic effect at most of the concentrations tested in strain TA100. Only the highest concentrations of ellagic acid reduced the mutagenic effect of MNU weakly and only in combination with two lower concentrations of MNU. In the micronucleus test, three-day oral application of ellagic acid prior to the applicaton of AFB1, IQ, or MNU, respectively, markedly reduced the numbers of micronuclei induced by these three mutagens in polychromatophilic erythrocytes of mice. Chemiluminescence test with mouse granulocytes proved that ellagic acid not only prevents the inhibitory effects of mutagens on free oxygen radicals and hydrogen peroxide production, but that this production is stimulated by ellagic acid in combination with mutagens even to a greater extent than by ellagic acid alone. From these results we can deduce that ellagic acid repairs strong immunosuppressive effects of all mutagens applied.

• MeSH
• aflatoxin B1 analogy a deriváty   MeSH
• antimutagenní látky * analýza   MeSH
• erytrocyty imunologie   MeSH
• imunosupresivní léčba MeSH
• kyselina ellagová * MeSH
• lidé MeSH
• luminiscence MeSH
• methylnitrosomočovina * MeSH
• mikrojaderné testy MeSH
• mutageny * MeSH
• myši inbrední BALB C MeSH
• Salmonella typhimurium MeSH
• statistika jako téma MeSH
• testy genotoxicity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

• Publikační typ
• abstrakt z konference MeSH

Práce se zabývá sledováním genotoxického rizika vybraných mykotoxinů (nivalenol, fusarenon X, kyselina penicilová) a jejich kombinací s aflatoxinem B1, který je znám jako silný mutagen. Tyto látky vznikají v potravinách sekundárně jako produkty mikroskopických hub kontaminujících potraviny. Mutagenní aktivita byla testována Amesovým testem na dvou kmenech bakterií Salmonella typhimurium a pomocí cytogenetické analýzy buněk kostní dřeně křečíka čínského (Cricetullus griseus). Mutagenní aktivita jednotlivých mykotoxinů V Amesově testu nebyla prokázána (s výjimkou aflatoxinu B1 s metabolickou aktivací), ale kombinace mykotoxinů s aflatoxinem B1 mutagenní aktivitu vykazovaly. U kombinací nivalenolu s aflatoxinem B1 a fusarenonu X s aflatoxinem B1 však byl účinek nižší než u samotného aflatoxinu, v některých koncentracích dokonce statisticky významně. Frekvenci aberantních buněk v kostní dřeni samců křečíka čínského zvyšoval statisticky významně fusarenom X a kyselina penicilová, zatímco frekvence aberantních buněk u skupiny zvířat ovlivněné nivalenolem se nelišila od hodnot skupiny kontrolní. Fusarenon X v kombinaci s aflatoxinem B1 indukoval statisticky významně zvýšené počty aberantních buněk oproti kontrolní skupině pouze u samců, nivalenol a AFB1 pouze u samic. Kombinace kyseliny penicilové s fusarenonem X vykazovala pouze nevýznamné zvýšení mutagenity oproti kontrole. Žádná z kombinací mykotoxinů nebyla statisticky významně odlišná od klastogenního účinku samotného aflatoxinu B1.

This work deals with the genotoxic risk of selected mycotoxins (nivalenol, fusarenon X, penicillic acid) and their combinations with aflatoxin B1, known as a potent mutagen. These substances may be produced by microscopical fungi as their secondary metabolites contaminated food. The mutagenic activity was tested by Ames test using two bacterial strains Salmonella typhimurium and by cytogenetic analysis of Chinese hamster bone marrow cells (CricetuUus griseus). Except mycotoxin aflatoxin B1, in the Ames test with metabolic activation, the mutagenic activity of tested mycotoxins was not recorded in contrast to combinations of tested mycotoxins with aflatoxin B1, The mutagenic activity of combinations of nivalenol with aflatoxin B1 and fusarenon Xwith aflatoxin B1 was significantly lower (in some concentrations) than aflatoxin B1 mutagenicity alone. The frequencies of aberrant bone marrow cells of Chinese male hamsters were significantly increased by fusarenon X or penicillic acid, whereas the frequencies of aberrant bone marrow cells of animals affected by nivalenol were the same as in the control group. The combination of fusarenon X with aflatoxin B1 induced a significantly higher frequency of aberrant cells only in males, the combination nivalenol with aflatoxin B1 only in females in comparison to the control group. The mutagenicity induced by penicillic acid and fusarenon X combination was insignificantly increased as compared to the control group. The tested mycotoxin combinations did not exhibit significantly different clastogenic effect as compared to aflatoxin B1 alone. Possible mechanisms of mycotoxin interactions are discussed.

• MeSH
• aflatoxin B1 aplikace a dávkování   metabolismus   škodlivé účinky   MeSH
• chromozomální aberace MeSH
• finanční podpora výzkumu jako téma MeSH
• křečci praví MeSH
• kyselina fusarová aplikace a dávkování   metabolismus   škodlivé účinky   MeSH
• kyselina penicilová aplikace a dávkování   metabolismus   škodlivé účinky   MeSH
• modely nemocí na zvířatech MeSH
• mykotoxiny chemie   metabolismus   škodlivé účinky   MeSH
• testy genotoxicity MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH