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Biomedical subjects

G Witz

Publications and source records attributed to G Witz.

At least 73 records · Page 4Linked to original sources
PubMed1986

Lipid composition of liver microsomes from rats treated with acetone.

The metabolism of certain compounds by rat hepatic microsomal preparations obtained from acetone-treated rats is greater than that measured in microsomes obtained from control rats. Since the lipid composition of membranes can significantly influence metabolism catalyzed by membrane-bound enzymes, studies were conducted in order to determine whether acetone-induced alterations in microsomal metabolism are associated with changes in the lipid composition of these membranes. Phospholipid and cholesterol concentrations were measured in extracts of rat liver microsomes obtained from rats treated with acetone, sodium phenobarbital, or vehicle. Acetone treatment did not alter the phospholipid and cholesterol content of the microsomes, whereas sodium phenobarbital (positive control) caused a significant decrease in cholesterol content/mg microsomal protein. These data indicate that acetone-induced alterations in microsomal metabolism may not be attributed to changes in the phospholipid and cholesterol content of the microsomes.

Acetone↗
PubMed1986

The reaction of 2-thiobarbituric acid with biologically active alpha,beta-unsaturated aldehydes.

The standard assay for lipid peroxidation is the measurement of the pink, 532 nm absorbing chromogen which is formed upon reaction of 2-thiobarbituric acid (TBA) with the lipid peroxidation product malonaldehyde (MDA). The present studies indicate that the toxic lipid peroxidation product trans-4-hydroxynonenal and its dehydration product trans,trans-nonadienal react with TBA to form chromogens which absorb maximally at 530 and 532 nm, respectively. Other biologically active alpha,beta-unsaturated aldehydes, such as acrolein and crotonaldehyde, short-chain homologs of alkenals formed during lipid peroxidation, and trans,trans-muconaldehyde, a novel diene dialdehyde, react with TBA to form products which absorb maximally at 495 nm. The molar extinction coefficients of the aldehyde:TBA chromogens formed were found to vary widely, suggesting that only small contributions to the 532 nm absorption by TBA adducts of reactive aldehydes other than MDA may be encountered during the use of the TBA assay.

Aldehydes↗
PubMed1986

Formation of muconaldehyde, an open-ring metabolite of benzene, in mouse liver microsomes: an additional pathway for toxic metabolites.

It has been proposed that a ring-opened form may be responsible for the toxicity of benzene. The present studies demonstrate that incubation of [14C]benzene with liver microsomes (obtained from male CD-1 mice treated with benzene) in the presence of NADPH results in the formation of a ring-opened product. Evidence for the identity of this product was obtained by derivatizing with 2-thiobarbituric acid (TBA), which resulted in the formation of an adduct with a 490-nm absorbance maximum. This maximum is identical to that observed after authentic trans,trans-muconaldehyde has reacted with TBA. Separation of muconaldehyde, both with and without trapping with TBA, from other benzene metabolites in the incubation mixture was accomplished by HPLC. The radioactivity profile of fractions collected during HPLC analysis contained peaks that eluted with muconaldehyde and the muconaldehyde-TBA adduct. The structure of the ring-opened product was confirmed by mass spectrometry, studies in which the HPLC peak from the microsomal incubation mixture that eluted at the retention time of authentic muconaldehyde was collected and derivatized with 2,4-dinitrophenylhydrazine. The high-resolution mass spectrum of this sample contained an ion with an m/z of 291.0729, corresponding to muconaldehyde mono-dinitrophenylhydrazone. These results indicate that benzene is metabolized in vitro to a ring-opened product identified as muconaldehyde.

Aldehydes↗
PubMed1986

Phorbol diacetate inhibits superoxide anion radical production and tumor promotion by mezerein.

The ability of the non-promoter phorbol diacetate (PDA) to modulate superoxide anion radical production by the complete tumor promoter phorbol myristate acetate (PMA) or the second stage promoter mezerein was assessed. Superoxide anion radical production was measured by the superoxide dismutase inhibitable reduction of nitroblue tetrazolium (NBT) to a blue intracellular formazan precipitate. These studies demonstrated that superoxide anion radical production by murine peritoneal exudate cells (PEC) stimulated by i.p. injection with mezerein (100 ng) is inhibited in a dose-dependent manner by co-administration with PDA (1-1000 ng). There was no effect on the number of formazan-positive PEC when PDA was co-administered with PMA. In a two-stage tumor promotion bioassay in female SENCAR mice initiated with 25.6 micrograms dimethylbenz[a]anthracene (DMBA) followed by first stage promotion with PMA (4X, 2 micrograms), co-administration of mezerein (2 micrograms) with 2 micrograms or 20 micrograms PDA reduced the number of papillomas after 14 weeks by 38% and 44%, respectively, compared with mezerein treatment alone. PDA (20 micrograms) when co-administered with mezerein (2 micrograms) does not inhibit mezerein induced hyperplasia in mouse skin. These results suggest a correlation between the ability of PDA to inhibit both superoxide anion radical production and tumor promotion by mezerein.

Animals↗
PubMed1986

Ozone acts alone and synergistically with ionizing radiation to induce in vitro neoplastic transformation.

Ozone, a major chemical oxidant in the atmosphere, is an environmental air pollutant whose ability to act as a direct carcinogen is unclear Using in vitro transformation, a technique which permits the study of oncogenesis in the absence of host specific effects, we report for the first time that ozone (5 p.p.m. for 5 min) induces neoplastic transformation in vitro in both primary hamster embryo cells and mouse fibroblast cultures (C3H/10-1/2). Exposure of the hamster and mouse cells to ozone also results in enhanced levels of free radical-mediated lipid peroxidation products. We also report for the first time on the carcinogenic interaction between ozone and ionizing radiation. Exposure of the cells to 3 or 4 Gy of gamma-rays, 2 h prior to O3 treatment, results in markedly enhanced rates of transformation, statistically consistent with a synergistic interaction between the agents. The results demonstrate that O3 acts as a direct carcinogen and co-carcinogen on susceptible cells, therefore having important consequences for public health.

Cell Line↗
PubMed1986

Estimation of risk of glucose 6-phosphate dehydrogenase-deficient red cells to ozone and nitrogen dioxide.

It has been suggested that the more than 1 million black Americans with the A- variant of glucose-6-phosphate dehydrogenase deficiency (G6PD) are at risk for adverse hematologic effects due to inhalation of ambient levels of oxidant gases. To evaluate this hypothesis studies were performed that included direct exposure of human G6PD-deficient red cells, and of mouse strains with different G6PD levels, to the oxidant gases ozone and nitrogen dioxide. Using the oxidant drug phenylhydrazine in part as a point of comparison, conservative extrapolation of the data indicates that exposure to levels of ozone or nitrogen dioxide at least one and probably two orders of magnitude above the LD50 would be required for any hematologic effect to be observed of pertinence to G6PD deficiency. It is concluded that there is no reason to remove or preclude from the workplace black employees with the common A- variant of red cell G6PD deficiency who potentially are exposed to oxidant gases.

Animals↗
PubMed1985

[Peritoneovenous shunt in ascites therapy. Complications and their treatment].

Complications occurred in 29 of 37 patients after ascites retransfusion (n = 16) or introduction of a peritoneovenous shunt (n = 21). Blood clotting disturbances, that could either be successfully treated with drugs or which led to interruption of the reinfusion, appeared in 38%. Estimation of plasminogen proved to be of reliable prognostic value thus enabling prophylactic measures to be taken. Post-operatively 14 patients had transient fever not requiring specific treatment. Local fibrinolysis or shunt revision was successful in three patients with shunt thromboses. According to our experience most complications can be avoided by prophylactic and therapeutic measures.

Adult↗
PubMed1985

Short-term toxicity of trans,trans-muconaldehyde.

Toxicological and biochemical effects of muconaldehyde, a six-carbon diene dialdehyde, were evaluated in 6- to 9-week-old CD-1 male mice. The LD50 of trans,trans-muconaldehyde was 6.7 and 7.1 mg/kg body wt when calculated by two different methods. Administration of trans,trans-muconaldehyde (2 mg/kg, ip) daily for 10 and 16 days resulted in a statistically significant decrease in red blood cell count, hematocrit, hemoglobin, bone marrow cellularity, and hepatic total and free sulfhydryl content. There was an increase in white blood cell count and spleen weight at 16 days. Similar effects, but of much lesser magnitude, were observed when the mice were given the same total dose of 2 mg/kg divided into three daily ip injections of 0.67 mg/kg trans,trans-muconaldehyde for 10 and 16 days. This alpha,beta-unsaturated aldehyde is a potent bone marrow toxin in mice.

Aldehydes↗
PubMed1985

Muconaldehyde formation from 14C-benzene in a hydroxyl radical generating system.

It has recently been proposed that muconaldehyde, a six carbon, alpha, beta-unsaturated dialdehyde, may be a hematotoxic metabolite of benzene. The present studies indicate that trans, trans-muconaldehyde is formed from benzene in vitro in a hydroxyl radical (.OH) generating system containing ascorbate, ferrous sulfate and EDTA in phosphate buffer, pH 6.7. Muconaldehyde formed from benzene in the .OH generating system was identified by trapping it with thiobarbituric acid (TBA), which results in the formation of an adduct with a 495 nm absorption maximum and a 510 nm fluorescence emission maximum. These maxima were identical to those observed after reacting authentic trans, trans-muconaldehyde with TBA. This finding was supported by thin layer chromatography and solid phase extraction studies. In those studies benzene-derived muconaldehyde cochromatographed with the muconaldehyde/TBA standard. Analyses of the products from the .OH generating system using high performance liquid chromatography (HPLC) confirm that trans, trans-muconaldehyde is a product of benzene ring fission. Regardless of whether or not TBA was used for trapping, samples from the .OH system incubated with benzene contained a peak which cochromatographed with the muconaldehyde standard. The radioactivity profile of fractions collected during HPLC analysis demonstrates 14C-benzene to be the source of the trans, trans-muconaldehyde. The role of hydroxyl radicals in the formation of muconaldehyde was investigated by using dimethyl sulfoxide, mannitol, and ethanol as .OH scavengers. These scavengers, at concentrations of 10 and 100 mM, were found to cause a dose-dependent decrease in the formation of muconaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehydes↗
PubMed1985

Thirteen cationic ionophores: their acute toxicity, neurobehavioral and membrane effects.

Thirteen cationic ionophores (12-Crown-4, 15-Crown-5, 18-Crown-6, Dibenzo 18-Crown-6, Dicyclohexano 18-Crown-6, 24-Crown-8, Dicyclohexano 24-Crown-8, Lasalocid, Hexacyclen trisulfate, Chiral binapthol, Valinomycin, Monensin, and A-23187) were evaluated for acute toxicologic properties, including lethality and neurobehavioral effects in multiple species (rats, rabbits, and mice) by multiple routes, skin and eye irritation and effects on membrane permeability to physiologic cations. Attention was focused on determining minimum neurobehavioral effect levels and characterizing the spectrum of these effects at different dose levels. While LD50's followed one pattern, this was not the case with other effects. Cluster and factor analysis suggest that, though the primary mechanism of action is alteration of membrane permeability to specifi-cations (qualitative types of activity correlate with the results of membrane permeability studies), which ions are provided an increased passage varies with ring size and charge dispersion. In the intact animal absorption markedly modifies these results.

Animals↗
PubMed1982

Enhancement of rat and human phagocyte superoxide anion radical production by cadmium in vitro.

The mechanism by which cadmium produced oxidizing effects in vivo is unknown. We show that cadmium enhances the production of superoxide anion radical (O-(2) .), a reactive oxygen species, in digitonin-stimulated phagocytes from man and rat. Cadmium concentrations ranging from 3.6 X 10(-2)M to 3.6 X 10(-4)M inhibited O-(2) . production in rat alveolar macrophages or human granulocytes. However, when activated in the presence of 3.6 X 10(-5)M cadmium, the production of O-(2) . was increased by a factor of 2.11 +/- 0.25 above control levels in human granulocytes and 3.6 +/- 0.62 above control levels in rat alveolar macrophages. This effect by levels of cadmium within the range of those occurring during in vivo toxicity might provide an explanation for the oxidizing effects of this metal ion.

Animals↗
PubMed1981

Stimulation of human polymorphonuclear leukocyte superoxide anion radical production by tumor promoters.

Comparison was made of the ability of the potent tumor promoter phorbol myristate acetate (PMA), as well as less active PMA analogs and non-phorbol ester tumor promoters, to stimulate superoxide anion radical (O-.2) production by human polymorphonuclear leukocytes (PMN). The rate of O-.2 production was found to correlate with the tumor-promoting activity of the phorbol esters as opposed to their inflammatory activity. Mezerein and telocidin B were slightly better stimulators of O-.2 production than PMA. Acetic acid was inactive. These data are discussed in terms of a possible role for O-.2 and other reactive oxygen species in tumor promotion.

Humans↗