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Toxicology, pharmacology and immunotherapy

Head of Department: RNDr. Miroslav Machala, CSc.

tel.: +420 5 3333 1801
e-mail: machala__(at)__vri.cz

Nejvýznamnější publikace:

IN VITRO STUDIES 

Machala M., Ulrich R., Vondráček J., Rubeš J., Šrám R.J.: Presence of environmental toxicants in semen and blood of young men from the Teplice region, Czech Republic. Environ. Epidemiol. Toxicol. 2, 24-31, 2000.

Vondráček J., Machala M., Minksová K., Bláha L., Murk A.J., Kozubík A., Hofmanová J., Hilscherová K., Ulrich R., Ciganek M:, Neča J., Švrčková D., Holoubek I.: Monitoring river sediments contaminated predominantly with polycyclic aromatic hydrocarbons by chemical and in vitro bioassay techniques. Environ. Toxicol. Chem. 20, 1499-1506, 2001.

Hilscherová K., Kannan K., Kang Y.-S., Holoubek I., Machala M., Masunaga S., Nakanishi J., Giesy J.P.: Characterization of dioxin-like activity of sediments from a Czech river basin. Environ. Toxicol. Chem., 20, 2768-2777, 2001.

Machala M., Vondráček J., Bláha L., Ciganek M., Neča J.: Aryl hydrocarbon receptor-mediated activity of mutagenic polycyclic aromatic hydrocarbons determined using in vitro reporter gene assay. Mutat. Res. 497, 49-62, 2001.

Machala M., Ciganek M., Bláha L., Minksová K., Vondráček J.: Aryl hydrocarbon receptor- mediated and estrogenic activities of oxygenated polycyclic aromatic hydrocarbons and azaarenes originally identified in extracts of river sediments. Environ. Toxicol. Chem. 20, 2736-2743, 2001.

Bláha L., Machala M., Vondráček J., Breineková K.: Multiple oxidative stress parameters are modulated in vitro by oxygenated polycyclic aromatic hydrocarbons identified in river sediments. Adv. Exp. Med. Biol. 500, 225-228, 2001.

Bláha L., Kapplová P., Vondráček J., Upham B., Machala M.: Inhibition of gap-junctional intercellular communication by environmentally occurring polycyclic aromatic hydrocarbons. Toxicol. Sci. 65, 43-51, 2002.

Machala M., Bláha L., Vondráček J., Lehmler H.-J., Robertson L.W., Malmberg T.: Comparison of relative toxic potencies of hydroxylated PCBs and quinones in hepatic and mammary cell lines. Organohalogen Compounds 56, 25-28, 2002.

Vondráček J., Kozubík A., Machala M.: Modulation of estrogen receptor-dependent reporter construct activation and G0/G1-S-phase transition by polycyclic aromatic hydrocarbons in human breast carcinoma MCF 7 cells. Toxicol. Sci. 70, 193-201, 2002.

Machala M., Bláha L., Vondráček J., Trosko J.E., Scott J., Upham B.L.: Inhibition of gap junctional intercellular communication by noncoplanar polychlorinated biphenyls: Inhibitory potencies and screening for potential mode(s) of action. Toxicol. Sci., 76, 102-111, 2003.

Machala M., Bláha L., Lehmler H.-J., Plíšková M., Májková Z., Kapplová P., Sovadinová I., Vondráček J., Malmberg T., Robertson L. W.: Toxicity of hydroxylated and quinoid PCB metabolites: inhibition of gap junctional intercellular communication and activation of aryl hydrocarbon and estrogen receptors in hepatic and mammary cells. Chem. Res. Toxicol., 17, 340-347, 2004.

Chramostová K., Vondráček J., Šindlerová L., Vojtěšek B., Kozubík A., Machala M.: Polycyclic aromatic hydrocarbons modulate cell proliferation in rat hepatic epithelial stem-like WB-F344 cells. Toxicol. Appl. Pharmacol., 196, 136-148, 2004.

Vondráček J., Chramostová K., Plíšková M., Bláha L., Brack W., Kozubík A., Machala M.: Induction of aryl hydrocarbon receptor-mediated and estrogen receptor-mediated activities and modulation of cell proliferation by dinaphthofurans. Environ. Toxicol. Chem. 23, 2214-2220, 2004.

Ciganek M., Neca J., Adamec V.,. Janosek J., Machala M.: A combined chemical and bioassay analysis of traffic-emitted polycyclic aromatic hydrocarbons. Sci. Total Environ. 334-335, 141-148, 2004.

Vondráček J., Machala M., Bryja V., Chramostová K., Krčmář P., Dietrich C., Hampl A., Kozubík A.: Aryl hydrocarbon receptor-activating polychlorinated biphenyls and their hydroxylated metabolites induce cell proliferation in contact-inhibited rat liver epithelial cells. Toxicol. Sci. 83, 53-63, 2005.

Plíšková M., Vondráček J., Vojtěšek B., Kozubík A., Machala M.: Deregulation of cell proliferation by polycyclic aromatic hydrocarbones in human breast carcinoma MCF-7 cells reflects both genotoxic and nongenotoxic events. Toxicol. Sci. 83, 246-256, 2005.

Plíšková M., Vondráček J., Canton R.F., Neča J., Kočan A., Petrík J., Trnovec T., Sanderson J.T., van den Berg M., Machala M.: Impact of polychlorinated biphenyls contamination on estrogenic activity in human male serum. Environ. Health Perspect. 113, 1277-1284, 2005.

Andrysík Z., Machala M., Chramostova K., Hofmanová J., Kozubík A., Vondráček J.: Activation of ERK1/2 and p38 kinases by polycyclic aromatic hydrocarbons in rat liver epithelial cells is associated with induction of apoptosis. Toxicol. Appl. Pharmacol. 211, 198-208, 2006.

Vondráček J., Švihálková-Šindlerová L., Pěnčíková K., Krčmář P., Andrysík Z., Chramostová K., Marvanová S., Valovičová Z., Kozubík A., Gábelová A., Machala M.: 7H-Dibenzo[c,g]carbazole and 5,9-dimethyldibenzo[c,g]carbazole exert multiple toxic events contributing to tumor promotion in rat liver epithelial ‘stem-like’ cells. Mutat. Res. 596, 43-56, 2006.

Andrysík Z., Vondráček J., Machala M., Krčmář P., Švihálková-Šindlerová L., Kranz A., Weiss C., Faust D., Kozubík A., Dietrich C.: The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells. Mutat. Res. (Fundamental and Molecular Mechanisms of Mutagenesis) 615, 87-97, 2007.

Švihálková-Šindlerová L., Machala M., Pěnčíková K., Marvanová S., Neča J., Topinka J., Sevastyanova O., Kozubík A., Vondráček J.: Dibenzoanthracenes and benzochrysenes elicit both genotoxic and nongenotoxic events in rat liver ‘stem-like’ cells. Toxicology 232, 147-159, 2007.

Zatloukalová J., Švihálková-Šindlerová L., Kozubík A., Krčmář P., Machala M., Vondráček J.: ß-Naphthoflavone and 3’-methoxy-4’nitroflavone exert ambigous effects on Ah receptor-dependent cell proliferation and gene expression in rat liver ‘stem-like’ cells. Biochem. Pharmacol. 73, 1622-1634, 2007.

Vondráček J., Švihálková-Šindlerová L., Pěnčíková L., Marvanová S., Krčmář P., Ciganek M., Neča J., Trosko J., Upham B., Kozubík A., Machala M.: Concentrations of methylated naphthalenes, anthracenes, and phenanthrenes occuring in Czech river sediments and their effects on toxic events associated with carcinogenesis in rat liver cell lines. Environ. Toxicol. Chem. 26, 2308-2316, 2007.

Umannová L., Zatloukalová J., Machala M., Krčmář P., Májková Z., Hennig B., Kozubík A., Vondráček J.: Tumor necrosis factor-? modulates effects of aryl hydrocarbon receptor ligands on cell proliferation and expression of cytochrome P450 enzymes in rat liver “stem-like“ cells. Toxicol. Sci. 99, 79-89, 2007.

Topinka J., Marvanová S., Vondráček J., Sevastyanova O., Nováková Z., Krčmář P., Pěnčíková K., Machala M.: DNA adducts formation and induction of apoptosis in rat liver epithelial ‘stem-like’ cells exposed to carcinogenic polycyclic aromatic hydrocarbons. Mutat. Res. (Fundamental and Molecular Mechanisms of Mutagenesis) 638, 122-132, 2008.

Courter L.A., Musafia-Jeknič T., Ciganek M., Machala M., Baird W.M.: Inhibition of CYP1A1 and CYP1B1 enzymes by aromatic compounds adsorbed on urban dust particulate matter. Polycyclic Arom. Comps. 27, 185-196, 2007.

Marvanová S., Vondráček J., Pěnčíková K., Trilecová L., Krčmář P., Topinka J., Milcová A., Machala M.: Toxic effects of methylated benz[a]anthracenes in liver cells. Chem. Res. Toxicol., 21, 503–512, 2008.

Upham B., Bláha L., Babica P., Park J.-S., Sovadinová I., Pudrith C., Rummel A.M., Weis L.M., Sai K., Tithof P.K., Gužvič M., Vondráček J., Machala M., Trosko J.E.: Inhibition of intercellular signaling, a tumor promotion event, by a cigarette abundant PAH, depends on phosphatidylcholine-specific phospholipase C. Cancer Sci., in press.

Machala M., Švihálková-Šindlerová L., Pěnčíková K., Krčmář P., Topinka J., Milcová A., Nováková Z., Kozubík A., Vondráček J.: Effects of methylated chrysenes on AhR-dependent and –independent toxic events in rat liver epithelial cells. Toxicology, in press.

Umannová L., Machala M., Topinka J., Nováková Z., Milcová A., Kozubik A., Vondracek J.: Tumor necrosis factor-? potentiates genotoxic effects of benzo[a]pyrene in rat liver epithelial cells through upregulation of cytochrome P450 1B1 expression. Mutat. Res. (Fundamental and Molecular Mechanisms of Mutagenesis), 640, 162-169, 2008.

Brack W, Schmitt-Jansen M, Machala M, Brix R, Barceló D, Schymanski E, Streck G, Schulze T.: How to confirm identified toxicants in effect-directed analysis. Anal. Bioanal. Chem., in press, 2008.

Umannová L., Neča J., Andrysík Z., Vondráček J., Upham B.L., Trosko J.E., Hofmanová J., Kozubík A., Machala M.: Non-dioxin-like polychlorinated biphenyls induce a release of arachidonic acid in liver epithelial cells: A partial role of cytosolic phospholipase A2 and extracellular signal-regulated kinases 1/2 signalling. Toxicology, in press, 2008.


REVIEWS

Machala M., Vondráček J.: Estrogenic activity of xenobiotics. Vet. Med.-Czech 43: 311-317, 1998.

Hofmanová J., Machala M., Kozubík A.: Epigenetic mechanisms of the carcinogenic effects of xenobiotics and in vitro methods of their detection. Folia Biol. (Prague) 46: 165-173, 2000.

Hilscherová K, Machala M, Kannan K, Blankenship AL, Giesy JP (2000): Cell bioassays for detection of aryl hydrocarbon (AhR) and estrogen receptor (ER) mediated activity in environmental samples. Environ. Sci. Pollut. Res. 7, 159-171.

Giesy J. P., Hilscherová K., Jones P.D., Kannan K., Machala M.: Cell bioassays for detection of aryl hydrocarbon (AhR) and estrogen receptor (ER) mediated activity in environmental samples. Mar. Pollut. Bull. 45, 3-16, 2002.


CHEMOPROTECTIVE AND/OR TOXIC EFFECTS OF POLYPHENOLS AND OTHER XENOBIOTICS/DRUGS

Machala M., Kubínová R., Hořavová P., Suchý V.: Chemoprotective potentials of homoisoflavonoids and chalcones of Dracaena cinnabari: modulations of drug-metabolizing enzymes and antioxidant activity. Phytotherapy Res. 15, 114-118, 2001.

Kubínová R., Machala M., Minksová K., Neča J., Suchý V.: Chemoprotective activity of boldine: modulation of drug-metabolizing enzymes. Pharmazie, 56, 242-243, 2001.

Kummer V., Mašková J., Čanderle J., Zralý Z., Neča J., Machala M.: Estrogenic effects of silymarin in ovariectomized rats. Vet. Med. - Czech, 46, 17-23, 2001.

Sovak M., Seligson A.L., Konas M., Hajduch M., Dolezal M., Machala M., Nagourney R.: Herbal composition PC-SPES for management of prostate cancer: identification of active principles. J. Natl. Cancer Inst. 94, 1275-1281, 2002.

Forejtníková H., Lunerová K., Kubínová R., Jankovská D., Marek R.Kareš R., Suchý V., Vondráček V., machala M.: Chemoprotective and toxic potentials of synthetic and natural chalcones and dihydrochalcones in vitro. Toxicology 208, 81-93, 2005.

Plíšková M., Vondráček J., Křen V., Gažák R., Sedmera P., Walterová D., Psotová J., Šimánek V., Machala M.: Effects of silymarin flavonolignans and synthetic silybin derivatives on estrogen and aryl hydrocarbon receptor activation. Toxicology 215, 80-89, 2005.

Procházka L., Turánek J., Tesařík R., Knötigová P., Polášková P., Andrysík Z., Kozubík A., Žák F., Sova P., Neužil J., Machala M.: Apoptosis and inhibition of gap-junctional intercellular communication induced by LA-12, a novel hydrophobic platinum(IV) complex Arch. Biochem. Biophys. 462, 54–61, 2007.


IN VIVO BIOMARKERS

Machala M., Mátlová M., Svoboda I., Nezveda K.: Induction effects of polychlorinated biphenyls, polycyclic aromatic hydrocarbons and other widespread aromatic environmental pollutants on microsomal mono-oxygenase activities in chick embryo liver. Arch. Toxicol., 70, 362-367, 1996.

Machala M., Nezveda K., Iriza A., Bu-Abbas A., Ioannides C.: Expression and inducibility of cytochrome P450 proteins in the liver of chick embryo. Arch. Toxicol., 71, 57-63, 1996.

Machala M., Neča J., Drábek P., Ulrich R., Šabatová V., Nezveda K., Raszyk J., Gajdůšková V.: Effects of chronic exposure to PCBs on cytochrome P450 systems and steroidogenesis in liver and testis of bulls (Bos taurus). Comp. Biochem. Physiol. 120A, 65-70, 1998.

Skálová L., Szotáková B., Machala M., Neča J., Souček P., Havlasová J., Wsól V., Křídová L., Kvasničková E., Lamka J.: Effect of ivermectin on activities of cytochrome P450 isoenzymes in mouflon (Ovis musimon) and fallow deer (Dama dama). Chem. Biol. Interact. 137, 155-167, 2001.

Machala M., Neča J., Ulrich R., Souček P., Lamka J., Szotáková B., Skálová L.: Inter-species comparisons of hepatic cytochrome P450 enzyme levels in male ruminants. Arch. Toxicol. 77, 555-560, 2003.

Szotáková B., Baliharová V., Lamka J., Nozinová E., Wsol V., Velík J., Machala M., Neca J., Souček P., Susová S., Skálová L.: Comparison of in vitro activities of biotransformation enzymes in pig, cattle, goat and sheep. Res. Vet. Sci. 76, 43-51, 2004.

Machala M., Petřivalský M., Nezveda K., Ulrich R., Dušek L., Piačka V., Svobodová Z.: Responses of carp hepatopancreatic 7 ethoxyresorufin O deethylase and glutathione-dependent enzymes to organic pollutants - a field study. Environ. Toxicol. Chem. 16, 1410-1416, 1997.

Petřivalský M., Machala M., Nezveda K., Piačka V., Svobodová Z., Drábek P.: Glutathione-dependent detoxifying enzymes in rainbow trout liver: search for specific biochemical markers of chemical stress. Environ. Toxicol. Chem. 16, 1417-1421, 1997.

Machala M., Drábek P., Neča J., Kolářová J., Svobodová Z.: Biochemical markers for differentiation of exposures to nonplanar polychlorinated biphenyls, organochlorine pesticides, or 2,3,7,8-tetrachlorodibenzo-p dioxin in trout liver. Ecotoxicol. Environ. Saf. 41, 107-111, 1998.

Machala M, Jurajda P, Neča J, Ulrich R, Štaffová K, Studničková Z, Dušek L, Holoubek I.: Biochemical responses to environmental contaminants in chub (Leuciscus cephalus) caught in the Morava river. Mar. Environ. Res. 46, 327-328, 1998.

Machala M, Ulrich R, Neča J, Vykusová B, Kolářová J, Máchová J, Svobodová Z.: Biochemical monitoring of aquatic pollution: Indicators of dioxin-like toxicity and oxidative stress in the roach (Rutilus rutilus) and chub (Leuciscus cephalus) in the Skalice river. Vet. Med.-Czech 45, 55-60, 2000.

Machala M, Hilscherová K, Kubínová R, Ulrich R, Vykusová B, Kolářová J, Máchová J, Svobodová Z.: Biochemical markers of dioxin-like toxicity and oxidative stress in hepatic microsomes of bream (Abramis brama) and perch (Perca fluviatilis) in the Elbe river. Vet. Med.-Czech 45, 195-199, 2000.

Machala M., Dušek L., Hilscherová K., Kubínová R., Jurajda P., Neča J., Ulrich R., Gelnar M., Studničková Z., Holoubek I.: Determination and multivariate statistical analysis of biochemical responses to environmental contaminants in feral freshwater fish Leuciscus cephalus L. Environ. Toxicol. Chem. 20, 1141-1148, 2001.

Machala M., Souček P., Neča J., Ulrich R., Lamka J., Szotáková B., Skálová L.: Inter-species comparisons of hepatic cytochrome P450 enzyme levels in male ruminants. Arch Toxicol. 77, 555-560, 2003.

Szotáková B., Baliharová V., Lamka J., Nozinová E., Wsól V., Velík J., Machala M., Neča J., Souček P., Sůsová S., Skálová L.: Comparison of in vitro activities of biotransformation enzymes in pig, cattle, goat and sheep. Res. Vet. Sci. 76, 43-51, 2004.

Kummer V., Mašková J., Zralý Z., Neča J., Šimečková P., Vondráček J., Machala M.: Estrogenic activity of environmental polycyclic aromatic hydrocarbons in uterus of immature Wistar rats. Toxicol. Lett., submitted.

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