A method of testing postnatal carcinogenicity in rats was elaborated. The substances to be tested were administered from the 1st day after birth to the 5th, 10th and 20th days of age. The subsequent supply of a substance in diet from weaning (28th day of age) up to the end of the first year of survival was an optimal combination. A total of 12 substances were tested by this method. For all substances it was possible to provide a comparison with the results of long-term studies. For nine substances carcinogenicity was demonstrated in both tests, out of them in eight cases in identical organ systems. In three cases no carcinogenicity was ascertained in the postnatal study, in two compounds identical negative results were obtained by the two approaches. In one case (the cytostatic TS-160) development of sarcomas was found at the site of subcutaneous administration in the long-term study, and this effect was not observed in the postnatal study. Results identical for the two methods (carcinogenic or noncarcinogenic) were achieved in 11 substances, i.e. 91.7%. In addition, in 10 compounds, for which carcinogenicity was demonstrated either in the postnatal study or in the long-term study, the occurrence of tumors was found in identical organ systems after 8 compounds which is an 80% agreement. In mice, this identity of organs was demonstrated only in 62.5% of the compounds tested. The present results demonstrated that the use of postnatal carcinogenicity test in rats offers the determination of possible carcinogenic effect of the compound tested with a high probability, under economically more advantageous conditions, and with almost the same qualitative results as with the use of the long-term tests for carcinogenicity.

• MeSH
• časové faktory MeSH
• druhová specificita MeSH
• experimentální nádory chemicky indukované   patologie   MeSH
• karcinogeny toxicita   MeSH
• krysa rodu Rattus MeSH
• myši MeSH
• novorozená zvířata MeSH
• stárnutí fyziologie   MeSH
• testy karcinogenity metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• karcinogeny MeSH

Mequindox (MEQ) is a synthetic antibacterial agent. Recent studies showed that MEQ and its primary metabolites exhibit strong genotoxicity to mammalian cells, and MEQ induced carcinogenicity in mice. These findings suggest that chronic exposure to MEQ could lead to an increased risk of cancer later in life. In the present study, four groups of Wistar rats (55 rats/sex/group) were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg) for 2 years. The results showed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive systems, were the main targets for MEQ. Liver toxicity mediated by MEQ was associated with apoptosis and the nuclear factor κB (NF-κB) signaling pathway. In addition, MEQ increased the incidence of tumors in rats. Phosphorylated histone H2AX (γ-H2AX) is identified as a biomarker of cellular response to DNA double-strand breaks (DSB). Our data demonstrated that γ-H2AX expression was significantly increased in tumors. Thus, high levels of DSB might be responsible for carcinogenesis in rats, and further investigation is absolutely required to clarify the exact molecular mechanisms for carcinogenicity caused by MEQ in vivo.

• Klíčová slova
• Apoptosis, Carcinogenicity, DNA damage, Mequindox, γ-H2AX,
• MeSH
• analýza přežití MeSH
• apoptóza účinky léků   MeSH
• chinoxaliny toxicita   MeSH
• dietární expozice MeSH
• experimentální nádory metabolismus   MeSH
• fosfoproteiny biosyntéza   MeSH
• histony biosyntéza   MeSH
• imunohistochemie MeSH
• játra účinky léků   metabolismus   MeSH
• karcinogeny toxicita   MeSH
• NF-kappa B metabolismus   MeSH
• poškození DNA * MeSH
• potkani Wistar MeSH
• tělesná hmotnost účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chinoxaliny MeSH
• fosfoproteiny MeSH
• gamma-H2AX protein, rat MeSH Prohlížeč
• histony MeSH
• karcinogeny MeSH
• Mequindox MeSH Prohlížeč
• NF-kappa B MeSH

• MeSH
• abnormality vyvolané léky etiologie   MeSH
• biotransformace MeSH
• embryo savčí účinky léků   MeSH
• karcinogeny toxicita   MeSH
• lidé MeSH
• metronidazol škodlivé účinky   metabolismus   farmakokinetika   toxicita   MeSH
• mutageny toxicita   MeSH
• poškození DNA MeSH
• těhotenství MeSH
• testy genotoxicity MeSH
• testy karcinogenity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• karcinogeny MeSH
• metronidazol MeSH
• mutageny MeSH

Cytoenzymological changes were observed in parasitic ciliates (Nyctotheroides puytoraci) and flagellates (Opalina sudafricana and Protoopalina sp.) after injection of their host, Bufo regularis, with a single dose of 0.5 mg beta-naphthylamine (BNA) per toad. The experiment was carried out during the host's pre-breeding season. Trophozoites of the given parasites were examined 21 days after the injection. The localization of the mitochondria and the relative intensity of succinic dehydrogenase (SDH) and deoxyribonucleic acid (DNA) activity in the control and BNA-treated trophozoites were compared. The results could prove useful for screening the carcinogenicity of chemicals by means of these parasitic protozoans.

• MeSH
• Eukaryota účinky léků   enzymologie   MeSH
• histocytochemie MeSH
• testy karcinogenity * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Changes in the Golgi bodies and in hydrolytic enzymes were observed in parasitic ciliates (Nyctotheroides puytoraci) and flagellates (Opalina sudafricana and Protoopalina sp.) after the administration of a single dose of 0.5 mg beta-naphthylamine (BNA) to their host, Bufo regularis. The experiment was carried out during the host's pre-breeding season, from November to February (when only trophozoites are available); the trophozoites were examined 21 days after the injection of BNA. Use of the silver impregnation technique showed an increase in the size of the granular argentophilic Golgi bodies in all three trophozoites after administering BNA to their host. In addition, a larger number of acid phosphatase and nonspecific esterase granules was found in the endoplasm of the three parasites after the injection. The localization of acid phosphatase and nonspecific esterase was found to be similar to the distribution of the Golgi bodies in both the control and the treated preparations. The results could be useful, in that some protozoans could be employed for the quick detection of chemical carcinogenicity if changes in their hydrolytic enzyme content are used as a diagnostic feature.

• MeSH
• Eukaryota účinky léků   enzymologie   MeSH
• ropuchy parazitologie   MeSH
• testy karcinogenity metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

This report reviews styrene biotransformation, including minor metabolic routes, and relates metabolism to the genotoxic effects and possible styrene-related carcinogenicity. Styrene is shown to require metabolic activation in order to become notably genotoxic and styrene 7,8-oxide is shown to contribute quantitatively by far the most (in humans more than 95%) to the genotoxicity of styrene, while minor ring oxidation products are also shown to contribute to local toxicities, especially in the respiratory system. Individual susceptibility depending on metabolism polymorphisms and individual DNA repair capacity as well as the dependence of the nonlinearity of the dose-response relationships in the species in question and the consequences for risk evaluation are analyzd.

• MeSH
• adukty DNA účinky léků   MeSH
• biotransformace MeSH
• DNA účinky léků   genetika   MeSH
• karcinogeny * MeSH
• lidé MeSH
• mutageny * MeSH
• poškození DNA účinky léků   MeSH
• styreny metabolismus   toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• adukty DNA MeSH
• DNA MeSH
• karcinogeny * MeSH
• mutageny * MeSH
• styreny MeSH

• MeSH
• Eukaryota účinky léků   MeSH
• karcinogeny * MeSH
• ropuchy parazitologie   MeSH
• testy karcinogenity MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• karcinogeny * MeSH

• MeSH
• chromozomální aberace MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• nežádoucí účinky léčiv * MeSH
• Salmonella typhimurium genetika   MeSH
• testy genotoxicity MeSH
• testy karcinogenity * MeSH
• výměna sesterských chromatid MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

2-Nitroanisole (2-NA) is an important industrial pollutant and a potent bladder carcinogen for rodents. The mechanism of its carcinogenicity was investigated in this study. Here we have used two independent methods, (32)P-post-labeling and (3)H-labeled 2-NA, to show that 2-NA binds covalently to DNA in vitro after reductive activation by human hepatic cytosol and xanthine oxidase (XO). We also investigated the capacity of 2-NA to form DNA adducts in vivo. Male Wistar rats were treated i.p. with 2-NA (0.15 mg/kg body wt daily for 5 days) and DNA from several organs was analyzed by (32)P-post-labeling. Two 2-NA-specific DNA adducts, identical to those found in DNA incubated with 2-NA and human hepatic cytosol or XO in vitro, were detected in the urinary bladder (3.4 adducts/10(7) nt), the target organ, and, to a lesser extent, in liver, kidney and spleen. The two DNA adducts found in rat tissues in vivo were identified as deoxyguanosine adducts derived from a 2-NA reductive metabolite, N-(2-methoxyphenyl)hydroxylamine. This reactive metabolite of 2-NA was identified in incubations with human hepatic cytosol, besides 2-methoxyaniline (o-anisidine). The results of our study, the first report on the potential of human cytosolic enzymes to contribute to the activation of 2-NA by nitroreduction, strongly suggest a carcinogenic potency of this rodent carcinogen for humans.

• MeSH
• adukty DNA * MeSH
• aldehydoxidasa metabolismus   MeSH
• aniliny metabolismus   MeSH
• anisoly farmakokinetika   toxicita   MeSH
• cytosol enzymologie   MeSH
• dítě MeSH
• DNA metabolismus   MeSH
• dospělí MeSH
• izotopy fosforu * MeSH
• játra účinky léků   enzymologie   MeSH
• karcinogeny farmakokinetika   toxicita   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   enzymologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• močový měchýř účinky léků   enzymologie   MeSH
• NAD(P)H dehydrogenasa (chinon) metabolismus   MeSH
• potkani Wistar MeSH
• předškolní dítě MeSH
• senioři MeSH
• slezina účinky léků   enzymologie   MeSH
• xanthinoxidasa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• krysa rodu Rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-anisidine MeSH Prohlížeč
• 2-nitroanisole MeSH Prohlížeč
• adukty DNA * MeSH
• aldehydoxidasa MeSH
• aniliny MeSH
• anisoly MeSH
• DNA MeSH
• izotopy fosforu * MeSH
• karcinogeny MeSH
• NAD(P)H dehydrogenasa (chinon) MeSH
• NQO1 protein, human MeSH Prohlížeč
• xanthinoxidasa MeSH

2-methoxyaniline (o-anisidine) is an industrial and environmental pollutant and a bladder carcinogen for rodents. The mechanism of its carcinogenicity was investigated with 2 independent methods, 32P-postlabeling and 14C-labeled o-anisidine, to show that o-anisidine binds covalently to DNA in vitro after its activation by human hepatic microsomes. We also investigated the capacity of o-anisidine to form DNA adducts in vivo. Rats were treated i.p. with o-anisidine (0.15 mg/kg daily for 5 days) and DNA from several organs was analyzed by 32P-postlabeling. Two o-anisidine-DNA adducts, identical to those found in DNA incubated with o-anisidine and human microsomes in vitro, were detected in urinary bladder (4.1 adducts per 10(7) nucleotides), the target organ, and, to a lesser extent, in liver, kidney and spleen. These DNA adducts were identified as deoxyguanosine adducts derived from a metabolite of o-anisidine, N-(2-methoxyphenyl)hydroxylamine. This metabolite was identified in incubations with human microsomes. With 9 human hepatic microsomal preparations, we identified the specific CYP catalyzing the formation of the o-anisidine metabolites by correlation studies and by examining the effects of CYP inhibitors. On the basis of these analyses, oxidation of o-anisidine was attributed mainly to CYP2E1. Using recombinant human CYP (in Supersomes) and purified CYPs, the participation of CYP2E1 in o-anisidine oxidation was confirmed. In Supersomes, CYP1A2 was even more efficient in oxidizing o-anisidine than CYP2E1, followed by CYP2B6, 1A1, 2A6, 2D6 and 3A4. The results, the first report on the potential of the human microsomal CYP enzymes to activate o-anisidine, strongly suggest a carcinogenic potential of this rodent carcinogen for humans.

• MeSH
• adukty DNA analýza   metabolismus   MeSH
• aniliny metabolismus   toxicita   MeSH
• biotransformace MeSH
• jaterní mikrozomy metabolismus   MeSH
• karcinogeny životního prostředí toxicita   MeSH
• krysa rodu Rattus MeSH
• látky znečišťující životní prostředí toxicita   MeSH
• oxidace-redukce MeSH
• potkani Wistar MeSH
• systém (enzymů) cytochromů P-450 fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-anisidine MeSH Prohlížeč
• adukty DNA MeSH
• aniliny MeSH
• karcinogeny životního prostředí MeSH
• látky znečišťující životní prostředí MeSH
• systém (enzymů) cytochromů P-450 MeSH