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Biomedical subjects

G Becher

Publications and source records attributed to G Becher.

At least 55 records · Page 3Linked to original sources
PubMed1988

Isolation and identification of mutagens from a fried Norwegian meat product.

Two samples of a typical Norwegian minced meat emulsion were fried at 215 degrees C. One had the regular composition while 4.2% creatine was added to the second sample prior to frying. Mutagens in both samples were purified using aqueous acid extraction, XAD-2 adsorption and a series of semipreparative and analytical high performance liquid chromatography (HPLC) purification steps monitored by the Ames/Salmonella mutagenicity test. Mutagenic activity in the creatine-fortified product was enhanced 15-fold. Mutagenicity profiles from reverse-phase and normal-phase HPLC were qualitatively similar for both samples indicating no major production of new mutagens due to the presence of additional creatine. A total of 8 distinct mutagenic peaks could be separated after three additional HPLC steps. These compounds fall into a class of compounds called amino-imidazoazaarenes (AIA). The majority of mutagenic activity is made up by the known cooking mutagens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), 2-amino-3-methylimidazo[3,5-f]quinoline (IQ) and 2-amino-n,n,n-trimethylimidazopyridine (TMIP). Smaller contributions are from 2-amino-3-methylimidazo- [4,5-f]quinoxaline (IQx), 2-amino-n,n-dimethylimidazopyridine (DMIP), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and two oxygen-containing AIA. With respect to mass, MeIQx and PhIP were the dominating mutagens.

Chromatography, High Pressure Liquid↗
PubMed1988

Genotoxic activity of the N-acetylated metabolites of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ).

The genotoxic potential of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and their N-acetylated metabolites (AcIQ and AcMeIQ, respectively) has been studied, in order to evaluate whether an initial N-acetylation of IQ or MeIQ is important for the overall in vivo genotoxicity of the compounds. When incubated with uninduced (control) rat hepatocytes, both the acetylated and the unacetylated compounds appeared to be relatively stable, whereas water-soluble metabolites (i.e. not extractable by ethyl acetate at alkaline pH) were rapidly formed with hepatocytes from PCB-induced animals. No DNA damage was induced by IQ or MeIQ in hepatocytes isolated from control rats, as measured by alkaline elution. In hepatocytes from PCB-pretreated rats, IQ, MeIQ, AcIQ and AcMeIQ induced DNA damage at low (10(-6) M) concentrations, with AcIQ being more potent than IQ whereas AcMeIQ was less potent than MeIQ. Similar patterns were observed when unscheduled DNA synthesis was measured in hepatocytes. The compounds induced sister chromatid exchanges in Chinese hamster V79 cells with PCB-induced hepatocytes as activation system; IQ and AcIQ were equal while AcMeIQ had less activity than MeIQ. The compounds were also compared in bacterial mutagenesis test systems (Salmonella typhimurium TA98). With hepatocyte activation, AcIQ was slightly more potent than IQ, whereas AcMeIQ was markedly less mutagenic than MeIQ. With subcellular fractions as activation system (rat liver S9 or microsomes), the N-acetylated compounds were similar to or less mutagenic than their parent compounds. The mutagenic effects of AcIQ and AcMeIQ in bacteria with microsomal activation were markedly reduced by the deacetylase inhibitor paraoxon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Respiratory failure caused by intratracheal saline: additive effect of xanthine oxidase.

Administration of physiological saline or drugs together with saline into the airways is becoming common clinical practice. However, there are few studies on possible side effects. We have studied the effects of saline, saline plus xanthine oxidase, and saline plus xanthine oxidase plus superoxidase dismutase on lung-thorax compliance and on arterial blood gases in anesthetized, paralyzed guinea pigs, ventilated for 2.5 h. Saline bolus (2-3 ml isotonic saline/kg body weight) into the airways reduced the compliance within 20 min to a mean of 39% of the pretreatment levels, and necessitated as increase in the respirator pressure. Saline plus xanthine oxidase decreased the compliance to 16% of the pretreatment levels. The xanthine oxidase-induced (but not saline-induced) decrease in lung compliance was relieved by superoxide dismutase. According to the present results xanthine oxidase induces a lung injury possible by production of free oxygen radicals. Superoxide dismutase can be valuable in prevention of free oxygen radical-mediated lung damage. Saline alone can be harmful when applied to the airways. This should be considered in clinical trials and in clinical practice.

Animals↗
PubMed1988

Experimental bronchoalveolar lavage in guinea pigs--a useful tool to investigate the intrabronchial release of substance P.

Bronchoalveolar lavage was performed in guinea pigs during bronchial challenge with capsaicin (100 micrograms/kg b.w. intravenously) and in control animals. Capsaicin caused a bronchoconstriction (VT minimal: 27.17% +/- 24.49). There was a significant amount of substance P-like immunoreactivity, detected by RIA in the lavage fluid of four of five animals challenged with capsaicin, but only in one of five controls. These results indicate that SPLIR is released into the bronchial lumen during capsaicin-induced bronchoconstriction. So bronchoalveolar lavage may be a useful tool to investigate the role of substance P in the bronchoconstrictor response induced by various stimulants.

Animals↗
PubMed1987

Acute and chronic effects of xanthine oxidase on lung thorax-compliance in guinea pigs.

Xanthine oxidase was given intratracheally in a single dose to guinea pigs. Lung compliance was measured after 4 h and 14 days respectively. Lung-thorax compliance was significantly lower compared with saline-treated controls both 4 h and 14 days after application of fluid. At 14 days there was a dose-related response between lung-thorax compliance and xanthine oxidase administered in the range 0-1.0 U. Superoxide dismutase (SOD) had a protective effect on xanthine oxidase action at 4 h, but not after 14 days. We suggest that the decreased lung-thorax compliance was caused by superoxide radicals, produced by the hypoxanthine-xanthine oxidase system, damaging lung tissue. We speculate that free oxygen radicals produced by the hypoxanthine-xanthine oxidase system could be an important contributory pathogenetic factor in producing both acute and chronic lung damage in, for instance, premature babies or adults, with respiratory distress syndrome.

Animals↗
PubMed1987

Fluorometric detection of 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and their N-acetylated metabolites excreted by the rat.

A sensitive fluorometric method has been developed for the determination of carcinogenic amino imidazoazaarenes (AIA compounds) which are formed during the cooking of food. They are separated by t.l.c. followed by spraying with dimethylsulfoxide and visualization by long-wave u.v. light. Quantification is done by fluorescence scanning. This method was applied to the determination of the metabolites in urine and feces from rats given 5 mg/kg body wt i.p. of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). Metabolites extractable by organic solvents were identified as the parent compound and their N-acetylated derivatives (AcIQ, AcMeIQ). Between 0.1 and 1% of the administered dose was recovered as these metabolites in urine during 24 h. The amounts of MeIQ and AcMeIQ found in feces were approximately 1 and 3% respectively. AcIQ was not detected in feces while IQ, MeIQ and their N-acetylated derivatives were found in bile. The metabolites in urine were identified by m.s. and in feces by t.l.c. and their fluorescent properties. When IQ or MeIQ were incubated with rat liver cytosol in the presence of acetyl-CoA, N-acetylated derivatives were formed. The reverse reaction, deacetylation, also took place in the liver cytosol, with Km values of 67 and 32 microM for AcIQ and AcMeIQ respectively.

Acetylation↗
PubMed1987

Studies on the mechanism of acetamide hepatocarcinogenicity.

The hepatocarcinogen acetamide, in single doses of 100 and 400 mg/kg b.wt., was shown to act as an initiator in a dose-dependent fashion in rat liver using the Solt-Farber method. Acetamide and its putative metabolite N-hydroxy-acetamide did not cause liver necrosis in single dose experiments. Acetamide showed no evidence for genotoxicity in tests for mutations in Salmonella typhimurium, for DNA damage in rat hepatoma cells or for DNA repair in isolated rat hepatocytes. In contrast, N-hydroxy-acetamide displayed genotoxic activity in all 3 test systems. Neither acetamide nor N-hydroxy-acetamide induced transformation of primary Syrian hamster embryo cells or gave evidence of inhibition of metabolic cooperation in V79 cells. Radiolabelled acetamide and N-hydroxy-acetamide were not bound covalently to proteins in the presence of various metabolic activation systems (microsomes plus NADPH or xanthine/xanthine oxidase, cytosol or cytosol plus acetyl CoA or proline plus ATP). N-Hydroxy-acetamide was cytotoxic to monolayers of isolated hepatocytes at concentrations above 2.5 mM. This cytotoxicity was increased after diethyl maleate treatment, but N-hydroxy-acetamide did not deplete cellular glutathione. A HPLC system was developed for the separation and quantification of acetamide, N-hydroxy-acetamide and acetic acid. No significant excretion of N-hydroxy-acetamide or acetic acid in the urine could be demonstrated after treatment of rats with 100 or 1,000 mg/kg b.wt. of acetamide. The underlying mechanism for the observed initiating effect of acetamide is obscure.

Acetamides↗
PubMed1987

A new conventional and high-frequency ventilator for small animals.

A pressure limited, time controlled ventilator has been designed especially for studies on experimental animals with severe respiratory distress syndrome (SRDS). Inspiration: Expiration (I:E) ratio (1:99-99:1) and frequency can be changed independently. Frequency ranged from 1 to 199/min in conventional ventilation (CV), while in high-frequency jet ventilation (HFJV) from 1 to 30 Hz. The gas delivery system consists of 3 magnetic valves (inspiration, expiration and HFJV, respectively) to ensure superposition of CV with HFJ or to use them separately. A monitoring unit switches off inspiration gas sources during HFJV if intratracheal pressure exceeds the alarm threshold. The device has been used in the following animal models: premature newborn rabbits with surfactant deficient lungs, emphysematous rats and guinea pigs as well as dogs and rabbits with SRDS due to lung lavage. Ventilation was most effective with an I:E ratio of 4:1 during pressure controlled CV, whereas during HFJV optimum gas exchange could be maintained with an I:E ratio of 1:4 and a frequency of 15 Hz in beagle dogs and 10 Hz in rabbits, respectively.

Animals↗
PubMed1986

Determination of polycyclic aromatic hydrocarbons in the urine, benzo(a)pyrene diol epoxide-DNA adducts in lymphocyte DNA, and antibodies to the adducts in sera from coke oven workers exposed to measured amounts of polycyclic aromatic hydrocarbons in the work atmosphere.

Workers in coke oven plants have a higher incidence of lung cancer than the general population. They are exposed to a variety of chemicals, in particular the polycyclic aromatic hydrocarbons (PAH), including benzo(a)pyrene. To evaluate the genotoxic effects of PAH exposure, air samples and urine samples were analyzed for PAH by capillary gas chromatography and high-performance liquid chromatography, respectively. Since benzo(a)pyrene is activated to 7 beta,8 alpha-dihydroxy-(9 alpha,10 alpha)-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) and binds to DNA, we have used ultrasensitive enzymatic radioimmunoassay and synchronous fluorescence spectrophotometry to measure BPDE-DNA adducts in lymphocyte DNA. The results show that workers were exposed to high concentrations of atmospheric PAH. However, the mean PAH exposure levels are reduced 60% when the workers wore masks during work. When compared to exposure levels, the urinary excretion of PAH was relatively low. Approximately one-third of the workers had detectable putative BPDE-DNA adducts in lymphocytes by ultrasensitive enzymatic radioimmunoassay, and 10% of the samples had emission peaks at 379 nm by synchronous fluorescence spectrophotometry. The four most positive samples were the same in both of the assays. Antibodies to an epitope(s) on BPDE-DNA were found in the sera of approximately one-third of the workers. Detection of DNA adducts and antibodies to these adducts are internal indicators of exposure to benzo(a)pyrene.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1985

Lung surfactant prevents allergic bronchial constriction in ovalbumin sensitized guinea pigs.

The stimulation of intrabronchial mast cells and macrophages by inhaled allergens play a major role in allergic bronchial asthma. Bronchial surfactant is proposed to change cell surface receptor response in the bronchial tree. In this investigation natural surfactant was found to reduce bronchial obstruction after intratracheal ovalbumin challenge in artificially ventilated guinea pigs sensitized to ovalbumin. After ovalbumin challenge tidal volume decreased to 59.2 +/- 14 % of the control value in surfactant treated animals. In solvent treated and untreated control animals, tidal volume decreased to 18.8 +/- 11% and 18.1 +/- 11% of the control value, respectively.

Aerosols↗
PubMed1984

Mutagenicity testing of high performance liquid chromatography fractions from wood stove emission samples using a modified Salmonella assay requiring smaller sample volumes.

Organic extracts of emissions from wood combustion have been fractionated by high performance liquid chromatography (HPLC) into 25-28 fractions. Each fraction was tested for mutagenic activity in a modified Ames Salmonella/microsome bioassay requiring one-third of the test volumes needed for the ususal test. Direct mutagenic activity was noted predominantly in the most polar fractions, whereas indirect mutagenic activity was associated with the fractions containing polycyclic aromatic hydrocarbons (PAH) and with polar fractions probably consisting of aza-arenes and aromatic amines.

Air Pollutants↗
PubMed1984

Short-term bioassays of fractionated emission samples from wood combustion.

Extracts of an emission sample from wood burning, consisting of particles and volatiles, have been fractionated on an HPLC silica gel column into five fractions of increasing polarity. Nonfractionated samples and the individual fractions have been tested in three different short-term bioassays: the Ames Salmonella assay, the sister chromatid exchange (SCE) induction-test in Chinese hamster ovary cells (CHO), and the cell transformation test on Syrian hamster embryo (SHE) cells. Most of the total activity was found in the volatile part of the sample with all three bioassays, whereas the particle extract had the highest activity per unit mass extracted. The second most polar fraction contained most of the mass and was also highly active in all assays. The most polar fraction was very potent in the Salmonella assay, but showed only a weak response in the eukaryotic bioassays. Storage of the samples for several months at 0 degrees C revealed that the bacterial mutagens present in the most polar fraction were labile; the mutagenicity was almost totally lost after 1 year's storage.

Animals↗
PubMed1984

Multimethod determination of occupational exposure to polycyclic aromatic hydrocarbons in an aluminum plant.

Occupational exposure to polycyclic aromatic hydrocarbons (PAH) in an aluminum smelter has been characterised simultaneously by three different techniques. Air samples were collected by personal sampling and analysed by capillary gas chromatography. Urine samples of exposed workers and a control group, smokers and non-smokers, were collected after shift and analysed for PAH and PAH-metabolites by reversed metabolism and high performance liquid chromatography using fluorescence detection. Blood samples were collected from the same persons and the frequency of sister chromatid exchange (SCE) in the lymphocytes determined. The results showed that workers are exposed to very high concentrations of PAH. This high exposure is not reflected in significantly different values of excreted PAH metabolites or in SCE when comparing exposed to non-exposed workers. However, differences between smokers and non-smokers are easily identified both in exposed and non-exposed workers.

Adult↗