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Biomedical subjects

P Vodicka

Publications and source records attributed to P Vodicka.

48 records · Page 3Linked to original sources
PubMed1991

32P-postlabeling of N-7, N2 and O6 2'-deoxyguanosine 3'-monophosphate adducts of styrene oxide.

Adducts were prepared by reacting styrene oxide with 2-deoxyguanosine 3'-monophosphate (dGMP). Four isomeric N-7-, two diastereomeric N2- and three isomeric O6-adduct were isolated and characterized. The adducts were used as substrates in the 32P-postlabeling reaction. No phosphorylation products were seen with the N-7-alkylation products. One diastereomeric N2-adduct was labeled with 20% efficiency and the second with a markedly lower efficiency. Two of the three O6-adducts were labeled with 5% and the third with 10% labeling efficiency. The results suggest that large N-7-dGMP adducts are very poor substrates of T4 polynucleotide kinase. The diastereomeric products are labeled at different efficiencies indicating stereoselectivity in the kinase reaction.

Deoxyguanine Nucleotides↗
PubMed1990

Effects of inhaled acrylic acid derivatives in rats.

Chemical reactivity with glutathione, urinary thioether excretion, total (T-SH) and non-protein-SH (NP-SH) groups in tissues and blood glucose were studied in male Wistar rats exposed to acrylic acid derivatives. The 6-h inhalation of acrylonitrile (AN), methyl acrylate (MA), ethyl acrylate (EA), n-butyl acrylate (BA) and 2-ethylhexyl acrylate (2-EHA) in several concentrations increased the urinary thioether excretion; the portion metabolized to thioethers was 35-18% of the acrylonitrile dose, but only 1.5-8% for the acrylates. Total-SH levels in the liver significantly decreased after the inhalation of AN, EA, BA and 2-EHA. In blood there was a decrease only after EA. Most pronounced NP-SH depletion was in the liver, less in blood and moderate in brain and lungs. There was an exponential relationship between the tissue NP-SH and the inhaled concentrations. Calculated concentrations inducing 50% NP-SH depletion indicated that reaction of acrylic acid derivatives with SH groups was decreasing in the order AN much greater than 2-EHA greater than EA = BA for the chemicals and liver greater than blood greater than lungs greater than brain for the tissues. All inhaled acrylates induced hyperglycemia, but acrylic acid was without effect. The chemical reactivity of acrylates with glutathione (GSH) decreased in the order EA greater than BA greater than MA greater than AN greater than 2-EHA. The results suggest that GSH depletion may participate in acute lethal and biochemical toxic effects of acrylic acid esters.

Acrylates↗
PubMed1990

The influence of N-7 platination and methylation on the stability of deoxyguanosine and deoxyguanylyl-(3'-5')-deoxyguanosine.

The rates of degradation of N-7 platinated deoxyguanosine (dG) and deoxyguanylyl-(3'-5')-deoxyguanosine (dGpdG) were followed in 66 mM Tris-HCl (pH 7.4) at 100 degrees C. The half-life for the intramolecular cross-link of cis-diamminedichloroplatinum(II) (cis-Pt) between two neighboring guanines (Pt-dGpdG) was 86 min, and the half-life of the intermolecular cross-link of cis-Pt on two guanines (dG-Pt-dG) was 54 min. For comparison the half-lives of dGpdG and the N-7 methylated dGpdG (Me-dGpdG) were 636 min and 11 min, respectively. The end product of the degradation of dGpdG, Pt-dGpdG and dG-Pt-dG was guanine, while Me-dGpdG was degraded to 7-methylguanine. In the case of dG-Pt-dG the main reaction pathway was through the depurination of one of the deoxyguanosines; in the case of Pt-dGpdG the degradation occurred either through the cleavage of one of the N-glycosidic bonds or through the cleavage of one of the Pt-bonds.

Chromatography, High Pressure Liquid↗
PubMed1990

Synthesis and stability of 2'-deoxyguanosine 3'-monophosphate adducts of dimethyl sulfate, ethylene oxide and styrene oxide.

Deoxyguanosine 3'-monophosphate (dGMP) was alkylated at the 7-position by dimethyl sulfate, ethylene oxide and styrene oxide in aqueous media and glacial acetic acid, respectively, to yield reasonable quantities of the products, which were purified by HPLC. dGMP adducts are needed as standards for the 32P-postlabelling assay. The stability of the adducts was studied at 37 degrees and neutral pH. The half-lives of disappearance of 7-methyl-dGMP and the beta-isomers of the styrene oxide adducts were about 250 min; 7-hydroxy-ethyl-dGMP and the alpha-isomers of the styrene oxide adducts had respective half-lives of 340 and 440 min. In all cases the main degradation product was the corresponding guanine adduct. The results demonstrate considerable lability of the 7-alkylation products of dGMP which has to be taken into consideration in devising the 32P-postlabelling assay.

Alkylating Agents↗
PubMed1989

Depurination from DNA of 7-methylguanine, 7-(2-aminoethyl)-guanine and ring-opened 7-methylguanines.

DNA was reacted with dimethyl sulphate and ethyleneimine to afford respective 7-methylguanine and 7-(2-aminoethyl)guanine derivatives. The substituted DNA was boiled in 0.1 M NaCl containing 10 mM phosphate buffer (pH 7.0), and the release of 7-alkylguanines, guanine and adenine was followed. The half-lives of depurination were 1.5 and 4.1 min for 7-(2-aminoethyl)guanine and 7-methylguanine, respectively. 7-Methylguanine was released some 60 times faster than guanine and adenine. When 7-methylguanine-containing DNA was treated in alkali to cause imidazole ring-opening, two products were liberated by boiling the DNA solution. These products were released with apparent half-lives of 69 and 34 min. These ring-opened products isomerized to each other completely within 1 h at 37 degrees C. The isomers had an identical ultraviolet spectrum and they displayed a pKa of 9.8. When silylated and analysed in gas chromatography-mass spectroscopy the two isomers had an identical molecular weight and fragmentation pattern, consistent with a structural assignment as N5-methyl-N5-formyl-2,5,6-triamino-4-oxopyrimidine. Only one of the isomers appeared to be present on DNA; the isomerization took place when the ring-opened product was released into solution.

Animals↗
PubMed1988

Distribution and elimination of (14C)-2-ethylhexyl acrylate radioactivity in rats.

The fate of (14C)-2-ethylhexyl acrylate was studied in adult male Wistar rats given an intravenous (i.v.) or intraperitoneal (i.p.) injection of 10 mg/kg (0.054 mmol/kg). The elimination of radioactivity from blood was bi-exponential, irrespective of the route of (14C)-2-EHA administration or the age (weight) of the rats. The first phase half-lives after i.v. and i.p. administration in 4-month-old rats were 30 and 60 min, in 7-month-old rats 115 and 130 min, respectively. The corresponding values for the slow-phase were 5 and 6 h, and 14 and 14 h. Elimination of the radioactivity from tissues followed a pattern similar to that seen for blood. More than half of the administered radioactivity was exhaled as carbon dioxide. Exhalation of unchanged (14C)-2-EHA accounted for only 0.05% (i.v.) or 0.3% (i.p.) of the initial dose of radioactivity. The radioactivity excreted in the urine within the first 24 h post-treatment accounted for 7% (i.p.) or 14% (i.v.) of the initial dose, and only 2% was excreted as thioethers.

Acrylates↗
PubMed1988

Depurination and imidazole ring-opening in nucleosides and DNA alkylated by styrene oxide.

Styrene-7,8-oxide was reacted with guanosine and deoxyguanosine and four isomeric 7-alkylguanosines were isolated, two of each being substitutions through the alpha and beta carbon of styrene oxide. The diastereomeric adducts imidazole ring-opened at an identical rate but the alpha- and beta-adducts differed (half-lives 90 and 56 min, respectively, pH 10, 24 degrees C). The 7-beta alkyl-deoxyguanosine derivatives ring-opened at a six times slower rate, which was similar to 7-methyldeoxyguanosine. The diastereomeric guanosine products also depurinated at the same rate but the beta-derivatives depurinated faster than the alpha-derivatives (t1/2 35 vs. 79 min, respectively, pH 1, 70 degrees C). The differences in the ring-opening and depurination of the alpha- and beta-isomers corresponded to their respective pK alpha values (7.31-7.32 vs. 7.16-7.19). The 7-alkyldeoxyguanosine derivatives of styrene oxide depurinated equally fast as 7-methyldeoxyguanosine. By contrast, the depurination of 7-alkylguanine was 15 times slower in the single-stranded DNA and 55 times slower in the double-stranded DNA.

Alkylation↗
PubMed1988

Phosphodiester cleavage in apurinic dinucleotides.

Apurinic sites were introduced to dGpdG, dGpdT, dTpdG and pdGpdG by HCl hydrolysis and the cleavage of the phosphodiester bond was measured in the monobase dinucleotides by HPLC. The half-lives of apdG and apdT (a = apurinic nucleotide) were 30 min and the half-life of papdG was 21 min in 66 mM Tris (pH 7.4) and 100 degrees C. The half-lives of dGpa and dTpa were 228 and 408 min, respectively. In these compounds the cleavage of the phosphodiester bond was not the main reaction pathway as little 3'-dGMP and 3'-TMP was isolated. The half-life of dGpa was similar to that of dGMP indicating that both compounds break down primarily by depurination. The results show that the phosphodiester bond is cleaved predominantly at the 3' side of the apurinic sugar. Sodium hydroxide and piperidine increased the rate of chain cleavage.

Chromatography, High Pressure Liquid↗
PubMed1988

Identification of alkylation products of styrene oxide in single- and double-stranded DNA.

Radioactive styrene oxide was reacted with double- and single-stranded DNA and the binding products were characterized by HPLC after neutral hydrolysis and enzyme digestion of DNA. More products were formed in single-stranded DNA as compared with double-stranded DNA. In single-stranded DNA at least 95% of the adducts were guanine N-7-,N2- and O6-alkylation products; they were formed in proportions 54:33:12. In double-stranded DNA the respective proportion was 74:23:3.7, indicating a selective suppression of alkylation at atoms N2 and, particularly, O6 that take part in hydrogen bonding in double-stranded DNA. The alpha- and beta-isomers of 7-alkylguanine were formed in a similar proportion in single- and double-stranded DNA, indicating no steric hindrance.

Alkylation↗
PubMed1986

Biliary excretion and organ distribution of 14C radioactivity after 14C-2-ethylhexyl acrylate administration in rats.

Rats were intravenously administered (14C)-2-ethylhexyl acrylate at the dose 10 mg/kg or 50 mg/kg b. w. Biliary excretion of 14C-radioactivity was followed in 1-3 hour intervals within the first 24 hours after administration. The rats were then sacrificed and distribution of 14C-radioactivity was followed in some organs. Highest radioactivity was found in liver, less in the kidneys and the least in the brain. A significant increase of bile flow was observed. In the 24-hour intervals 2.2% of the dose was eliminated via bile at both dosages, most of it (83%) during the first 3 hours.

Acrylates↗
PubMedDate not supplied

Screening for conditions of public health importance in people arriving in Australia by boat without authority.

OBJECTIVE: To determine the prevalence of tuberculosis, hepatitis B carriage and markers of hepatitis C and HIV infection in people detained in immigration reception and processing centres in Australia. DESIGN AND SETTING: Eighteen-month survey of medical conditions of public health importance in people detained at the immigration reception and processing centres at Curtin and Port Hedland in Western Australia and Woomera in South Australia. PARTICIPANTS: 7000 detainees (5742 adults and 1258 children and teenagers aged < 18 years) between 1 January 2000 and 30 June 2001. MAIN OUTCOME MEASURES: People treated for active tuberculosis; issuing of health undertakings to report to a chest clinic for follow-up of inactive tuberculosis; and confirmation of hepatitis B carrier status or hepatitis C or HIV infection. RESULTS: Eleven people required treatment for tuberculosis (in nine the diagnosis was confirmed bacteriologically), representing a prevalence of 157 cases per 100,000 population. This rate is much higher than the incidence in Australia in 1998 of 4.93 cases per 100,000 population, but comparable with rates in the source countries. Health undertakings were issued to 973 people (13.9%). Of these, 682 (70.1%) were for inactive tuberculosis (26 in association with hepatitis B carriage or hepatitis C infection); and 156, 58 and two health undertakings were for hepatitis B carriage, and hepatitis C and HIV infection, respectively. CONCLUSIONS: The health-screening program at immigration reception and processing centres detects significant numbers of conditions of public health importance, enabling treatment and surveillance to the benefit of the people detained and the Australian community.

Adolescent↗