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B W Street

Publications and source records attributed to B W Street.

14 recordsLinked to original sources
PubMed1987

Formation and fate of nucleic acid and protein adducts derived from N-nitroso-bile acid conjugates.

14C-N-Nitrosoglycocholic acid (14C-NOGC) reacted with calf thymus DNA in vitro to give a number of carboxymethylated adducts (7-carboxymethylguanine [7-CMG], 3-carboxy-methyladenine [3-CMA] and O6-carboxymethylguanine [O6-CMG]). 7-CMG is excreted unchanged in urine, and its use as a marker for NOGC exposure was studied. Administration of 14C-NOGC results in a dose-dependent urinary excretion of 14C-7-CMG and in labelling of blood proteins, albumin and globin. The activity in albumin disappears in vivo, with a half-life very similar to that of albumin itself. The monitoring of carboxymethylated nucleic acid bases and proteins appears to be a useful way of monitoring endogenous formation of NOGC and related compounds.

Animals↗
PubMed1985

Trialkyl phosphorothioates and glutathione S-transferases.

Using a rat liver cytosol source of enzyme trialkyl phosphorothioates have been shown to be substrates of glutathione S-transferases. Using OSS-trimethyl phosphorodithioate (OSS-Me(O] and OOS-trimethyl phosphorothioate (OOS-Me(O] the methyl transferred to the sulphydryl of glutathione is that attached to phosphorus via an oxygen atom. Fractionation of liver cytosol has shown that although the bulk activity is due to the three isozymes (1-1; 3-4; 1.2), OSS-Me(O) is a general substrate for glutathione S-transferases. The specific activity is low compared with the substrates 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene.

Animals↗
PubMed1984

The neurotoxicity of trimethyltin chloride in hamsters, gerbils and marmosets.

Trimethyltin chloride (TMT) was given to Syrian hamsters, gerbils and marmosets, and the changes in the brain were studied 1 day to 7 weeks later by light and electron microscopy. Within the marmoset brain, TMT was found to be uniformly distributed, similar to that in the rat. In all three species, signs of poisoning included whole-body tremors and prostration, while death might occur in 3-4 days; in marmosets ataxia, agitation, aggression and occasional fits were also observed. Bilateral symmetrical neuronal necrosis and chromatolysis were seen in the majority, which involved the hippocampus, pyriform cortex, amygdaloid nucleus, neocortex, various brain stem nuclei and in marmosets the retina. The probably lethal dose of TMT in all three species is approximately 3 mg kg-1, while the LD50 for the rat is 12.6 mg kg-1. The lower figure is probably related to lack of binding to haemoglobin in contrast to the binding in the rat. TMT does not bind to human haemoglobin and thus the predicted lethal dose for humans may be about 3 mg kg-1 (15.1 mumol kg-1), while the dose required to produce neuronal damage could well be less.

Animals↗
PubMed1984

The binding of triethyllead to rat and cat hemoglobin.

Equilibrium dialysis experiments were carried out to determine the affinity constant and stoichiometry of the binding of triethyllead to rat and cat hemoglobin. The affinity constants were 4 X 10(5) M-1 and 4.5 X 10(5) M-1 for rat and cat hemoglobin, respectively, and 2 mol triethyllead combined with 1 mol hemoglobin. The previous report of a stoichiometry of 3 could not be confirmed (Byington et al., 1980).

Animals↗
PubMed1981

The action of 5-coordinate triorganotin compounds on rat liver mitochondria.

5-Coordinate tin compounds influence mitochondrial function in the same three ways as triorganotin compounds: (1) they inhibit the energy conservation system like oligomycin, (2) they cause a Cl-/OH- exchange across mitochondrial membranes and (3) at high concentrations they cause large scale swelling. Unlike other triorganotin compounds they inhibit (1) at much lower concentrations than (2) and are as effective as oligomycin. Thhe implications of these findings for the mechanism of reaction of organotins with proteins, enzymes and mitochondria are discussed.

Adenosine Triphosphate↗
PubMed1979

The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat.

Trimethyltin, when given by gavage to rats, has an LD50 of 12.6 mg/kg. Signs of poisoning include tremors, hyperexcitability, aggressive behavior, weight loss, and convulsions. After single (10 mg/kg) or repeated weekly doses (a maximum of four) of 4 mg/kg, rats, up to a survival time of 70 days, were perfusion-fixed for light microscopy. Trimethyltin was assayed in brain and blood in rats after similar treatments. Trimethyltin is cumulative and persistent and binds with high affinity to hemoglobin. Trimethyltin, unlike triethyltin, does not produce white matter edema in rats but does cause bilateral and symmetrical neuronal alterations involving the hippocampus (largely sparing the Sommer sector), pyriform cortex, amygdaloid nucleus, and neocortex. The earliest alteration was loss or dispersal of Nissl substance, then clumping of nuclear chromatin, followed by shrinkage and fragmentation of the nucleus within shrunken eosinophilic cytoplasm. These changes were associated with approximately 1.4 microgram trimethyltin/g wet weight in brain tissue 1 day after the second dose of 4 mg/kg or 2 days after a single dose of 10 mg/kg. Signs of poisoning gradually disappeared, and 4 rats surviving 70 days appeared normal, although their brains had severe damage with cell loss in the hippocampi and each pyriform cortex. Treatment of rats with trimethyltin, therefore, provides a chronic preparation with consistent lesions in the hippocampus of use in other behavioral and neuroanatomic studies. (Am J Pathol 97:59--82, 1979).

Animals↗
PubMed1977

Oxidative phosphorylation. Halide-dependent and halide-independent effects of triorganotin and trioganolead compounds on mitochondrial functions.

1. Each of five triorganotin and five triorganolead compounds was shown to perturb mithochondrial functions in three different ways. One is dependent and two are independent of Cl- in the medium. 2. Structure-activity relationships for the three interactions are described, and compounds suitable as tools for the separate study of each process are defined. 3. In a Cl- -containing medium trimethyltin, triethyltin, trimethyl-lead, triethyl-lead and tri-n-propyl-lead all produce the same maximum rate of ATP hydrolysis and O2 uptake; this rate is much less than that produced by uncoupling agents such as 2,4-dinitrophenol. 4. Increase in ATP hydrolysis and O2 uptake are measures on energy ultilization when triogranotin and triorganolead compounds bring about an exchange of external C1- for intramitochondrial OH- ions. Possible rate-limiting steps in this process are discussed. 5. In a C1- -containing medium ATP synthesis linked to the oxidation of beta-hydroxybutyrate or reduced cytochrone c is less inhibited by triethyltin or triethyl-lead than is ATP synthesis linked to the oxidation of succinate, pyruvate or L-glutamate. 6. The inhibition of ATP synthesis linked to the oxidation of both beta-hydroxybutyrate and reduced cytochrome c consists of two processes: one is a limited uncoupling and is C1- -dependent and the other is a C1- -independent inhibition of the energy-conservation system. 7. The different sensitivities to inhibition by triethyltin of mitochondrial functions involving the oxidation of beta-hydroxybutyrate and succinate are compared and discussed.

Adenosine Triphosphate↗
PubMed1971

Oxidative phosphorylation. The relation between the specific binding of trimethylytin and triethyltin to mitochondria and their effects on various mitochondrial functions.

1. A binding site (site 1) is present in mitochondria with affinity for trimethyltin and triethyltin adequate for a site to which they could be attached when the processes of energy conservation are inhibited. 2. The quantitative relationships between the binding of trimethyltin and triethyltin to site 1 and their effects on various mitochondrial functions have been examined. 3. ATP synthesis linked to the oxidation of pyruvate, succinate and intramitochondrial substrate, ATP synthesis and oxygen uptake (succinate or pyruvate as substrate) stimulated by uncoupling agents are all inhibited by trimethyltin and triethyltin; when inhibition is less than 50% the ratio (percentage inhibition)/(percentage of binding site 1 complexed) is approx. 10:1. 4. ATP synthesis linked to the oxidation of reduced cytochrome c (ascorbate+NNN'N'-tetramethyl-p-phenylenediamine), ATP hydrolysis and oxygen uptake in the presence of low concentrations of trimethyltin and triethyltin approach zero activity as the proportion of binding site 1 complexed approaches 100%. 5. Possible interpretations of these findings are discussed with reference to published arrangements for coupling of electron transport to ATP synthesis and also to our present knowledge of the chemical and biological specificity of trialkyltin compounds.

Adenosine Triphosphate↗
PubMed1970

Oxidative phosphorylation. The specific binding of trimethyltin and triethyltin to rat liver mitochondria.

1. The binding of trimethyltin and triethyltin to rat liver mitochondria was determined and the results were analysed by the method of Scatchard (1949). 2. One binding site (site 1) has the correct characteristics for the site to which trimethyltin and triethyltin are attached when they inhibit oxidative phosphorylation. For each compound the concentration of site 1 is 0.8nmol/mg of protein and the ratios of their affinity constants are the same as the ratio of the concentrations inhibiting oxidative phosphorylation. 3. Binding site 1 is present in a fraction derived from mitochondria containing only 15% of the original protein. In this preparation ultrasonication rapidly destroyed site 1. 4. Dimethyltin and diethyltin do not prevent binding of triethyltin to rat liver mitochondria, whereas triethyl-lead does. 5. Trimethyltin and triethyltin bind to mitochondria from brown adipose tissue and the results indicate a binding site 1 similar to that in rat liver mitochondria. 6. The advantages and limitations of this approach to the study of inhibitors are discussed.

Adipose Tissue, Brown↗