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B Schoket

Publications and source records attributed to B Schoket.

33 records · Page 2Linked to original sources
PubMed1990

Dose-related induction of rat hepatic drug-metabolizing enzymes by diuron and chlorotoluron, two substituted phenylurea herbicides.

Dose-related induction of various hepatic drug-metabolizing enzymes has been investigated after short-term treatment of rats by diuron and chlorotoluron, a dichlorinated and a monochlorinated phenylurea herbicide, respectively. Results suggest that 'saturation' of the induction system of benzo(a)pyrene monooxygenase, 7-ethoxycoumarin O-deethylase and 7-ethoxyresorufin O-deethylase activities may occur in the same range of the molar doses of both compounds, and with the dichlorinated herbicide at much higher activities. Induction of epoxide hydrolase, UDP-glucuronyltransferase and glutathione S-transferases also shows saturation curves in the function of molar doses. However, the structural difference is not reflected in the enhancement of enzyme activities.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1990

Formation of DNA adducts in the skin of psoriasis patients, in human skin in organ culture, and in mouse skin and lung following topical application of coal-tar and juniper tar.

Preparations of coal-tar and juniper tar (cade oil) that are used in the treatment of psoriasis are known to contain numerous potentially carcinogenic polycyclic aromatic hydrocarbons (PAH). Evidence of covalent binding to DNA by components of these mixtures was sought in a) human skin biopsy samples from 12 psoriasis patients receiving therapy with these agents, b) human skin explants maintained in organ culture and treated topically with the tars, and c) the skin and lungs of mice treated with repeated doses of the formulations following the regimen used in the clinic. DNA was isolated from the human and mouse tissues and digested enzymically to mononucleotides. 32P-Post-labeling analysis revealed the presence of aromatic DNA adducts in the biopsy samples at levels of up to 0.4 fmol total adducts/microgram DNA. Treatment of human skin in organ culture produced similar levels of adducts, while treatment with dithranol, a non-mutagenic therapeutic agent, resulted in chromatograms indistinguishable from those from untreated controls. In mouse skin, coal-tar ointment and juniper tar gave similar DNA adduct levels, with a similar time-course of removal: maximum levels (0.5 fmol/microgram DNA) at 24 h after the final treatment declined rapidly to 0.05 fmol/microgram at 7 d, thereafter declining slowly over the succeeding 25 d. However, while coal-tar ointment produced only very low levels of adducts in mouse lung (less than 0.03 fmol/microgram DNA), juniper tar produced adducts at a high level (0.7 fmol/microgram DNA) that were persistent in this tissue. These results provide direct evidence for the formation of potentially carcinogenic DNA damage in human and mouse tissue by components of these therapeutic tar preparations.

Administration, Topical↗
PubMed1990

Repair studies on methylated DNA of CHO cells.

DNA methylation pattern was investigated on Chinese hamster ovary (CHO) cells after treatment with N-(14C)-methyl-N-nitrosourea (14C-MNU). The main target was the N-7 position of guanine, exceeding the methylation in the O6 position of guanine by a factor of 8 and that in the N-3 position of guanine and adenine by a factor of 20. No DNA repair could be observed within 2 hours after methylation. Pretreatment of cells with gamma irradiation (7 rad) before application of MNU induced repair of N-7-methylguanine. This methylation product was decreased to about 50% within two hours, whereas the repair of the other methylated bases was not influenced. The analysis was carried out by high performance liquid chromatography after acid hydrolysis of isolated DNA. 14C-methylated products were determined by liquid scintillation counting.

Animals↗
PubMed1990

DNA adduct formation in human and mouse skin by mixtures of polycyclic aromatic hydrocarbons.

32P-Postlabelling analysis has been used to detect the formation in vivo of DNA adducts by components of complex mixtures of polycyclic aromatic hydrocarbons (PAHs) in coal-tar, creosote, bitumen, juniper tar, used engine oils and fuel exhaust condensates. The presence of DNA adducts derived from these agents has been investigated in mouse skin, in human skin explants maintained in short-term organ culture and in human skin in vivo, and the formation of many different PAH-DNA adducts was observed. Similar levels and patterns of adducts were found in DNA from human skin to those in mouse skin, which is known to be susceptible to the carcinogenic activity of PAH mixtures, thus demonstrating the potential hazard to man of epidermal contact with these materials.

Animals↗
PubMed1989

32P-postlabelling analysis of DNA adducts of benzo[a]pyrene formed in complex metabolic activation systems in vitro.

The influence of cytochrome P-450-linked monooxygenase, epoxide hydrolase, UDP-glucuronyltransferase and glutathione S-transferases on the metabolic activation of benzo[a]pyrene (BP) was studied by incubating BP with preparations of rat-liver microsomal and cytosolic fractions in the presence of exogenous DNA. 32P-Postlabelling analysis of the DNA revealed the presence of covalently bound adducts formed by BP, which were visualised as radioactive spots on autoradiographs of thin-layer chromatograms. The effects on the adduct profile of adding different combinations of 1,2-epoxy-3,3,3-trichloropropane (TCPO), UDP-glucoronic acid (UDPGA) and glutathione (GSH) to the incubation mixture were determined. As many as 14 different DNA adducts were resolved and quantitated on the chromatograms, the numbers and quantities of which varied within a large range depending on the incubation conditions. The influence of the enzyme inhibitor and cofactors on the adduct patterns reflects the complex effects of simultaneous enzyme interactions on the metabolic activation of BP.

Animals↗
PubMed1989

32P-postlabelling analysis of DNA adducts in the skin of mice treated with petrol and diesel engine lubricating oils and exhaust condensates.

Samples of unused or used petrol and diesel engine lubricating oils were applied to the shaved dorsal skin of 4- to 6-week-old male Parkes mice, either as a single treatment (50 microliters/mouse) or as four consecutive daily treatments (50 microliters/application). DNA isolated from the skin 24 h after the final treatment was digested to 3'-mononucleotides and analysed by 32P-postlabelling for the presence of aromatic adducts. Enhancement of sensitivity using butanol extraction or nuclease P1 digestion of the DNA hydrolysates led to the detection of up to eight adduct spots on polyethyleneimine-cellulose thin-layer chromatograms with samples of DNA from skin treated with used engine oils, at levels of 40-150 amol total adducts/micrograms DNA. Multiple treatments with the used oils gave rise to similar patterns of adducts in lung DNA. A single treatment of mouse skin with petrol engine exhaust condensate (50 microliters), or diesel engine exhaust condensate (50 microliters), containing 20 and 46 micrograms benzo[a]pyrene (BaP)/g respectively, gave rise to approximately 75 amol total adducts/micrograms DNA in skin. A significant proportion, 31 and 48% respectively, of the adducts formed by the petrol and diesel engine exhaust condensates co-chromatographed with the major BaP-DNA adduct, but with the used engine oils, only petrol engine oil, and not diesel engine oil, produced significant amounts of an adduct (22% of total) that corresponded to the BaP-DNA adduct.

Adenosine Triphosphate↗
PubMed1988

Formation of DNA adducts in human skin maintained in short-term organ culture and treated with coal-tar, creosote or bitumen.

Adult and foetal human skin samples maintained in short-term organ culture were treated topically with solutions of coal-tar, creosote or bitumen, then DNA was isolated and analysed by 32P-post-labelling for the presence of aromatic DNA adducts. Autoradiographs of the 32P-labelled adducts resolved on polyethyleneimine-cellulose tlc sheets revealed a band of radioactivity indicative of the formation of adducts by a large number of components in these complex carcinogenic mixtures. Single doses of the materials, similar to those used to initiate tumours in experimental animals, resulted in the formation of approximately 0.3 fmol total adducts/micrograms DNA. The levels of adducts formed in human skin are thus similar to those formed in mouse skin after administration of doses known to be carcinogenic to the latter. The results provide direct evidence of DNA damage in human skin by materials strongly suspected of being carcinogenic to humans, and point to a method for evaluating other complex mixtures of aromatic chemicals for their potential carcinogenic hazard.

Coal Tar↗
PubMed1988

Covalent binding of components of coal-tar, creosote and bitumen to the DNA of the skin and lungs of mice following topical application.

In order to assess the DNA damaging ability of complex carcinogenic mixtures, male Parkes mice were treated topically with solutions of (i) pharmaceutical coal-tar, (ii) creosote, a blend of coal-tar fractions or (iii) bitumen, a product of oil-refining. DNA was isolated from the treated skin and analysed by 32P-post-labelling. A band of radioactivity was obtained on polyethyleneimine--cellulose TLC indicating the formation of DNA adducts by a large number of different chemical compounds present in these fossil fuel products. The chromatographic properties of the adducts were broadly characteristic of those formed by polycyclic aromatic hydrocarbons. The levels of DNA binding were approximately 0.4 fmol total adducts/micrograms DNA 24 h after treatment for coal-tar and creosote and 0.09 fmol/micrograms DNA for bitumen treatment. The persistence of adducts in mouse skin following a single dose of either coal-tar or creosote was found to exhibit a phase of rapid removal, in which one half to two thirds of the initial levels of adducts, detected at 24 h after treatment, were removed by 7 days followed by a second phase in which one half to two thirds of the remainder was removed in the succeeding 25 days. When mice were treated topically with multiple carcinogenic doses of coal-tar, creosote or bitumen for up to 5 weeks, a steady accumulation of adducts was seen in skin DNA during the course of the treatment, approaching a steady-state level towards the end of the treatment period in some instances. A similar accumulation of adducts was also evident in lung DNA, the levels being approximately half those attained in skin. The results demonstrate the application of 32P-post-labelling to the detection of DNA adducts formed in vivo by complex carcinogenic mixtures of the type to which humans are exposed.

Administration, Topical↗
PubMed1985

Induction of rat hepatic drug metabolizing enzymes by substituted urea herbicides.

Effects of eight structurally closely related substituted urea herbicides were investigated on the induction of cytochrome P-450 dependent monooxygenase enzyme complex, as well as on two conjugating enzymes after short-term treatment of rats. Liver microsomal cytochrome P-450 content was induced approximately by 50%. Cytochrome P-450 dependent monooxygenase activities showed a great variety depending on the substrate and on the herbicide. Two-18-fold induction was detected with 7-ethoxycoumarin, while up to 8-fold induction was measured with benzo(a)pyrene. Aldrin epoxidase activities were increased up to 3-fold, and aminopyrine N-demethylase activities were only slightly different from the control level. UDP-glucuronyltransferase and glutathione S-transferase activities were enhanced up to 2-fold. The results indicate that chemical structure of the related substituted urea compounds, the number of halogen substituents on their phenyl group exert a strong influence on the induction of monooxygenases.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1979

[Square-wave polarographic determination of tin in products of the food processing industry].

A square-wave polarographic method suitable for measuring tin in canned products and raw materials for food industry was examined. After wet digestion of the sample tin was directly determined from the acidic stock solution gained. If 10 ml of the stock solution was equivalent to 1 g sample,--varying sensitivity of the instrument--tin could be determined in the range of 5 micrograms/g--400 micrograms/g with +/- 5% relative error. By increasing sensitivity of the instrument this range could be extended to as little as 0,5 micrograms tin/g sample. The optimal quantity of hydrochloric acid to be added to the sulphuric acid solution of the digested sample before the instrumental measurement was determined by means of model solutions. Examinations concerning interference of lead were also performed. It is established, that if the ratio of Sn/Pb is at least 4/1, lead does not interfere with the polarographic tin determination. If the ratio of Sn/Pb is 2/1 or 1/1 tin content can be calculated after measuring the height of the peak of lead in sulphuric acid electrolyte. The method was applied for several canned products and comparative tests were performed with the spectrophotometric method given in the Hungarian standard MSZ 3612/7-77.

Animals↗
PubMedDate not supplied

Detection of polycyclic aromatic hydrocarbon exposure damage using different methods in laboratory animals.

Benzo[a]pyrene, benzo[b]fluoroanthene and dibenzo[a,h]anthracene dissolved in a 1:2 mixture of dimethylsulphoxide (DMSO) and water were administered to two groups of female mice, each group containing 15 mice. The doses were administered orally (via gavage) at the respective rates of 1 and 100 micrograms kg-1 body weight five times per week for a period of 9 weeks. The influence of the polycyclic aromatic hydrocarbons (PAHs) was determined using the following methods: determination of DNA-PAH adducts, of chromosome injuries (micronucleus test), of induction of repair using the unscheduled DNA synthesis (UDS) test, and by examination of the DNA structure after nucleoid sedimentation. All the methods investigated provided evidence of a significant effect resulting from exposure to PAHs on the parameters examined. Following chronic exposure to PAHs, the formation of DNA-PAH adducts and injury to the genetic material, as well as the appearance of micronuclei (micronucleus test), the induction of unscheduled DNA synthesis (UDS test) and mutation of the DNA structure (nucleoid sedimentation), were demonstrated. The described methods therefore provide a means for the detection of genetic damage caused by PAH exposure in humans.

Administration, Oral↗
PubMedDate not supplied

Comparative investigation of antipyrine half-life and induction of cytochrome P-450 dependent monooxygenases in rats treated with phenylurea herbicides.

The short-term effect of three substituted phenylurea herbicides has been investigated on antipyrine plasma half-life in rats. Isoproturon was ineffective, while chlortoluron and diuron decreased the half-life significantly. There was a close correlation between antipyrine half-lives and induction of hepatic cytochrome P-450 dependent benzo(a)pyrene monooxygenase, 7-ethoxycoumarin O-deethylase and 7-ethoxyresorufin O-deethylase.

Animals↗
PubMedDate not supplied

Increased sensitivity for determination of polycyclic aromatic hydrocarbon-DNA adducts in human DNA samples by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA).

A competitive enzyme-linked immunosorbent assay (ELISA), the most frequently used immunoassay for the determination of polycyclic aromatic hydrocarbon-DNA adducts in human tissues, has been modified to achieve approximately a 6-fold increase in sensitivity. The new assay, a competitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) has utilized the same rabbit antiserum as the ELISA, antiserum elicited against DNA modified with benzo[a]pyrene. However, the alkaline phosphatase conjugate has been replaced with a biotin-europium-labeled streptavidin signal amplification system, and the release of europium into the solution forms a highly fluorescent chelate complex that is measured by time-resolved fluorometry. The DELFIA has achieved a 5- to 6-fold increase in sensitivity for measurement of DNA samples modified in vitro with benzo[a]pyrene, for cultured cells exposed to radiolabeled benzo[a]pyrene, and for human samples from occupationally exposed workers. The assay has been validated by comparison of adduct levels determined by DELFIA, ELISA, and radioactivity in DNA from mouse keratinocytes exposed to radiolabeled benzo[a]pyrene. Human lymphocyte DNA samples from 104 Hungarian aluminum plant workers were assayed by ELISA and compared to blood cell DNA samples from 69 Italian coke oven workers assayed by DELFIA. The standard curves demonstrated that the limit of detection of 4.0 adducts in 10(8) nucleotides for polycyclic aromatic hydrocarbon-DNA adducts by ELISA, using 35 micrograms of DNA/microtiter plate well, has been decreased to 1.3 adducts in 10(8) nucleotides by DELFIA, using 20 micrograms of DNA/microtiter well. If 35 micrograms of DNA were used in the DELFIA, the calculated detection limit would be 0.7 adducts in 10(8) nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗