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Biomedical subjects

I Brandt

Publications and source records attributed to I Brandt.

At least 91 records · Page 5Linked to original sources
PubMed1985

Epithelial binding of 1,2-dibromoethane in the respiratory and upper alimentary tracts of mice and rats.

The metabolism and binding of the volatile carcinogen 1,2-dibromo[14C]ethane (DBE) were studied in C57BL mice, Sprague-Dawley rats, and Fischer rats. As shown by the whole-body and light microscopic autoradiography with heated and/or extracted sections, a selective accumulation of metabolites occurred in a number of tissues, preferentially in the reported target tissues for DBE-induced lesions [i.e., in the nasal cavity, lung, forestomach, and liver (tumors) and the adrenal, testicle, liver, and kidney (nonneoplastic lesions)]. High levels of nonextractable metabolites were registered in the epithelia of the entire respiratory tract, the upper alimentary tract, the vagina, and the subepithelial glands of the olfactory mucosa. Lower levels of metabolites were observed in the liver, adrenal cortex, testicular interstitium, and kidney. Autoradiography of slices from various extrahepatic tissues incubated in vitro with DBE showed that most epithelia of the respiratory tract, upper alimentary tract, vagina, and the testicular interstitium have a marked ability to activate DBE to metabolites that become bound to the tissue. Further in vitro experiments, performed with S-1 fractions prepared from various tissues, indicated that the nasal mucosa was most active in transforming DBE to products which could not be extracted from the protein precipitate. It is proposed that tissue-selective metabolism and activation of DBE in the epithelia of the respiratory and upper alimentary tract are responsible for the observed DBE-induced lesions in these organ systems.

Animals↗
PubMed1985

Target cells for the polychlorinated biphenyl metabolite 4,4'-bis(methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl. Characterization of high affinity binding in rat and mouse lung cytosol.

When a tritium-labeled metabolite of polychlorinated biphenyls (PCB), 4,4'-bis[( 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl [(3H-MeSO2)2TCB] is administered intraperitoneally to rats, a selective labeling is registered in the apical cytoplasm of the nonciliated bronchiolar (Clara) cells of the lung as determined by microautoradiography of sections of methacrylate-embedded tissue. In vitro, (3H-MeSO2)2TCB binds with high affinity (Kd = 2.5-15 nM) and high capacity (Bmax = 30-70 pmol/mg of protein) to rat lung cytosol. Binding of (3H-MeSO2)2TCB to the high affinity sites is temperature dependent, reversible, and saturable. The sites seem to reside within a protein-like component, since proteolytic enzymes significantly reduce the binding. Physiochemical characterization of the (3H-MeSO2)2TCB-binding protein indicates a Stokes radius of 22 A and a sedimentation coefficient of 1.7 S and, on the basis of these parameters, an apparent molecular weight of 16,000 may be calculated. The binding entity has an apparent pI of 5.3 and elutes as a single radioactive peak from CM-Sepharose at 75 mM acetate. Binding with similar affinities (IC50 values, 4-65 nM) is shown to occur also with other PCB methyl sulfones, whereas only one PCB, 2,2',4,4'5,5'-hexachlorobiphenyl, competes for (3H-MeSO2)2TCB binding, but with a lower affinity (IC50 = 3 microM). Among other compounds tested, only progesterone and some derivatives thereof display an affinity for the (3H-MeSO2)2TCB-binding protein (IC50 values ranging from 1 to 10 microM). Lung cytosol shows by far the highest amount of specific (3H-MeSO2)2TCB binding. However, low but detectable amounts are also found in cytosolic preparations from prostate, kidney, and large intestine. Finally, (3H-MeSO2)2TCB also binds to an entity in mouse lung cytosol with the same physicochemical characteristics as that in rat lung cytosol and to a progesterone-binding protein purified from rabbit uterus (uteroglobin). It is concluded that rat lung contains a uteroglobin-like macromolecule with a pronounced affinity for at least certain PCB methyl sulfones, and it is suggested that this binding entity is responsible for the striking accumulation of such metabolites in lung tissue following administration of PCB to rats and mice.

Animals↗
PubMed1984

Disposition of some sulphur-containing hexachlorobenzene (HCB) metabolites: affinity of methylsulphonylpentachlorobenzene for the gray matter of brain, the lungs and the adrenal zona reticularis.

The distribution of methylsulphonylpentachloro-[14C]benzene (I), methylthiopentachloro-[14C]benzene (II), 1,4-bis(methylthio)tetrachloro-[14C]benzene (III) and 1,2,4-tris(methylthio)trichloro[14C]benzene (IV) was studied after intravenous injection in mice. The administration of I resulted in a rapid and selective accumulation of radioactivity in the gray matter of the brain, the lung and the zona reticularis of the adrenal cortex. In mice pretreated with metyrapone, or with high dose of unlabelled I, the radioactivity in the tissues was increased, whereas pretreatment with diethyl maleate did not change the disposition of I. In mice injected with II-IV no site of selective accumulation in the tissues was observed. Similarly to I, compounds II-IV were rapidly excreted in bile/faeces and urine. It is proposed that the sulphone group is essential for the high affinity of I for the brain, lung and adrenal cortex.

Adrenal Cortex↗
PubMed1983

Chlorinated paraffins: disposition of a highly chlorinated polychlorohexadecane in mice and quail.

Uniformly 14C-labelled 1-chloro-polychlorohexadecane (PCHD) of high chlorine content (69% w/w) was given to Japanese quail and to C57Bl mice perorally (p.o.) and intravenously (i.v.). The degradation of PCHD to 14CO2, measured during 8 h, was found to be minute (about 1% of dose) in both species after either route of administration. In mice 66 and 43% of dose was eliminated in the feces during 96 h following p.o. and i.v. administration, respectively; the urinary excretion was about 3% in both cases. In quail, the combined fecal and urinary excretion during 96 h after p.o. administration was 58% of dose. The autoradiographic distribution following p.o. administration showed some general similarities between mice and quail; high radioactivities were present in bile, liver, kidney, and intestinal contents up to 24 h after administration. In addition, in quail high radioactivity was present in the hypophysis, retina, blood, and egg yolk. In mice strong accumulation and retention was observed in the corpora lutea up to 30 days after administration. A long time retention in fat occurred in both species.

Animals↗
PubMed1983

A simple method for collecting 14CO2 in fish.

A simple apparatus was designed for continuous collection of excreted 14CO2 in fish. Carp (Cyprinus carpio; body wt. about 400 g) were intraarterially injected with [14C]acetate (44 mmol) and transferred to a test chamber (21 +/- 1 degrees C). Within 48 h, 65.4 +/- 2.7% of the dose was recovered as 14CO2. A small amount of 14CO2 was retained in the water of the test chamber. Control experiments using [14C]acetate-injected mice as '14CO2-generators' showed that this 14C residue in the water could be recovered almost completely as 14CO2 upon acidification. In the carp experiments, some radioactivity remained in the acidified test chamber water; this residue may represent unchanged [14C]acetate and/or metabolites other than 14CO2.

Acetates↗
PubMed1983

Chlorinated paraffins: disposition of a polychloro-[1-14C]-hexadecane in carp (Cyprinus carpio) and bleak (Alburnus alburnus).

The disposition of polychloro-[1-14C]hexadecane (PCHD, 34% chlorine w/w) was studied in carp (Cyprinus carpio) and bleak (Alburnus alburnus). After intra-arterial (i.a.) injection in carp about 6% of dose was excreted as 14CO2 in 96 h. The autoradiographic distribution pattern after administration of PCHD to carp (i.a.) and bleak (up to 14 days of exposure in PCHD-contaminated water) was characterized by a strong labelling in the bile/intestinal contents. High radioactivity also appeared in the kidney, liver, gills and, particularly in bleak, in the nasal cavity, lens and skin.

Animals↗
PubMed1983

Distribution of the carcinogenic tryptophan pyrolysis product Trp-P-1 in control, 9-hydroxyellipticine and beta-naphthoflavone pretreated mice.

Autoradiograms obtained 1-4 h after i.v. injection of the 14C-labelled carcinogenic tryptophan pyrolysis product Trp-P-1 to albino and pigmented mice showed a pronounced uptake of radioactivity in the lymphatic system (thymus, lymph nodes, bone marrow and spleen), in the endocrine system (hypophysis, thyroid, adrenal medulla) and in the liver, kidney medulla and brain. High radioactivity was present in the excretory pathways, predominantly in the bile/intestinal contents. At longer post-injection times (24 h to 6 days) most of the labelled substance had left the tissues, except for the liver which still retained a high concentration of radioactivity. Trp-P-1 is known to be activated by cytochrome P-448. The uptake of radioactivity in the liver could be reduced by pretreatment with the cytochrome P-448 inhibitor 9-hydroxyellipticine suggesting that the observed accumulation of radioactivity in the liver was partly due to metabolites of Trp-P-1. After pretreatment with the cytochrome P-448 inducer beta-naphthoflavone, the administration of Trp-P-1 resulted in a highly selective accumulation of radioactivity in the lung parenchyma, exceeding all other tissues in the body. beta-Naphthoflavone pretreatment also increased the uptake of radioactivity in the kidney cortex and small intestinal mucosa. As indicated by a high labelling of the pigmented tissues of the maternal and fetal eye, the carcinogen and/or its metabolites were accumulated in melanin.

Alkaloids↗
PubMed1983

Placental transfer of hexachlorophene (HCP) in the marmoset monkey (Callithrix jacchus).

Autoradiography was used to study the distribution of 2,2'-14C-methylene-bis-(3,4,6-trichlorophenol) (HCP) in pregnant marmoset monkeys in early (day 30-50) and late (around day 120) gestation and in a newborn (11 days old) pup. Radioactivity was present in the conceptus at all stages of gestation, although the foetal concentration was lower than the maternal. In the embryo an accumulation was observed in the neural tube and in the embryonic membranes. In the late foetus and newborn monkey the highest concentration of radioactivity was found in the liver and the intestinal contents. The brain of the adult and newborn animals showed low concentration. A partial blood-brain barrier was present in the late foetus but, in relation to other tissues, the foetal brain concentration was higher than that of the mother.

Animals↗
PubMed1983

Metabolism of the mercapturic acid of 2,4',5-trichlorobiphenyl in rats and mice.

2,4',5-Trichloro[14C]biphenyl mercapturic acids (triCB-MA) were metabolized in part to methylsulphide, methylsulphoxide and methylsulphone metabolites after i.p., i.v. (hepatic portal vein) and p.o. administration to rats. Methylthio-triCB and triCB-MA were present in faeces and 3- and 4- methylsulphonyl-triCB (triCB-SO2CH3) were present in carcasses of all rats. Only triCB-SO2CH3 was present in lung tissue. As shown by autoradiography, radioactivity accumulated in the tracheo-bronchial mucosa of mice given either intracaecal or tail-vein injections of triCB-MA. Radioactivity extracted from the lungs of mice was shown to be present as triCB-SO2CH3.

Acetylcysteine↗
PubMed1982

Metabolic fate of chlorinated paraffins: degree of chlorination of [1-14C]-chlorododecanes in relation to degradation and excretion in mice.

The disposition of three [1-14C]-chlorododecanes (MCDD, PCDD I and PCDD II; 17.4%, 55.9%, and 68.5% chlorination) was studied in C57Bl mice. [1-14C]-lauric acid (LA) was studied as reference compound. Fifty-two percent (MCDD), 32% (PCDD I), and 8% (PCDD II) of the radioactive doses were exhaled as 14CO2 during 12 h after i.v. injection. Similar results were obtained after p.o. administration. In addition to a marked labelling of the liver and fat, the distribution patterns observed at 24 h after administration revealed an uptake of radioactivity in tissues with high cell turnover/high metabolic activity, e.g., intestinal mucosa, bone marrow, salivary glands and thymus. The concentration of radioactivity in these sites and the exhalation of 14CO2, which were inverse to the degree of chlorination, indicate that the chloroalkanes are degraded to metabolites which can be utilized in the intermediary metabolism. A similar, although more pronounced, distribution pattern and 14CO-2-exhalation (70% of i.v. dose) was observed after LA administration. The long time retention of heptane-soluble radioactivity in liver and fat (indicating unmetabolized substance) increased with degree of chlorination. On the contrary, the administration of LA and the chlorododecanes MCDD and PCDD I, but not of PCDD II, resulted in a selective labelling of the central nervous system 30-60 days after injection.

Adipose Tissue↗
PubMed1982

Metabolism of 2,4'5-trichlorobiphenyl: enrichment of hydroxylated and methyl sulphone metabolites in the uterine luminal fluid of pregnant mice.

Autoradiography of 2,4',5-trichloro-[14C] biphenyl ([14C] triCB) in mice at different stages of gestation indicated a strong accumulation of radioactivity in the uterine luminal fluid at gestation day 9 and later. From day 10 an uptake of radioactivity occurred also in the yolk sac epithelium. In order to identify the suspected metabolites in the fluid pregnant mice were dosed with unlabelled triCB on gestation day 9. Gas chromatographic (GC) and mass fragmentographic (MF) analysis of extracts of uterine fluid obtained on day 12 showed that hydroxylated, methyl sulphone and conjugated metabolites were present in the fluid. The unchanged triCB could not be detected in the extracts of the fluid. The site of release of the metabolites to the fluid may be the endometrium or, possibly, the yolk sac epithelium. The mechanism behind the concentration of water-insoluble methyl sulphone and hydroxylated metabolites of triCB in an aquatic phase is discussed.

Animals↗
PubMed1982

Metabolism of 2,4',5-trichlorobiphenyl: role of the intestinal microflora in the formation of bronchial-seeking methyl sulphone metabolites in mice.

Groups of germ-free and conventional mice were treated with 2,4',5-trichlorobiphenyl (triCB) and [35S]cysteine or [35S]methionine, respectively. Control animals received the labelled amino acids only. Conventional mice accumulated significantly more extractable radioactivity both in lung and kidney tissues when compared to germ-free mice. The extracted radioactivity in lung and kidney tissues was shown to be due to the accumulation of methyl-[35S]sulphonyl-triCB. The low radioactivity in lungs of the germ-free mice was also shown to be due to the accumulation of small amounts of the sulphones. The results indicate an involvement of the intestinal flora in the formation of methyl sulphone metabolites of triCB.

Animals↗
PubMed1982

Metabolism of 2,4',5-trichlorobiphenyl: tissue concentrations of methylsulphonyl-2,4',5-trichlorobiphenyl in germfree and conventional mice.

Whole-body autoradiography of 2,4',5-[14C]trichlorobiphenyl ([14C]triCB) indicated that, whereas there was accumulation of radioactivity in the tracheobronchial mucosa of conventional (C) mice 1-7 days after injection, no such effect was observed in germfree (GF) mice 1 day after injection. At days 4 and 7 there was a low, but significant, uptake by the tracheobronchial mucosa of the GF mice. Chemical analysis showed that the concentrations of 4-methylsulphonyl-triCB (4-MeSO2-triCB) in lung, kidney and liver 7 days after administration of triCB were 6.5, 14.7 and 3.7 times higher, respectively, in C than in GF mice. The results are interpreted as indicating the existence of a major metabolic route to triCB methyl sulphones involving the intestinal microflora, and a minor route, not requiring the flora.

Animals↗
PubMed1982

Selective affinity of dimethyl sulphoxide (DMSO) and 2-amino-4-phenylsulphonylbenzenesulphonamide (NSD 3004) for the large intestinal mucosa of mice.

Whole-body autoradiography of 14C-labelled dimethyl sulphoxide and 35S-labelled 2-amino-4-phenylsulphonylbenzenesulphonamide revealed a selective accumulation of labelled substance in the large intestinal mucosa of mice. The mechanism of accumulation is discussed with regard to previous results on sulphone-containing compounds with tissue-specific distribution patterns.

Animals↗
PubMed1982

Metabolism of 2,2',5,5'-tetrachlorobiphenyl: formation of mono- and bis-methyl sulphone metabolites with a selective affinity for the lung and kidney tissues in mice.

1. Distribution in mice of 2,2',5,5'-tetrachloro[14C]biphenyl has been studied by autoradiography. Radioactivity was specifically localized in the bronchial epithelium, the lung parenchyma, the kidney cortex and the adipose tissue. 2. Bis(methylsulphonyl)-2,2',5,5'-tetrachlorobiphenyl, a hitherto unknown metabolite of 2,2',5,5'-tetrachlorobiphenyl, has been identified in lung, kidney and liver of mice. 3- and 4-Methylsulphonyl-2,2'5,5'-tetrachlorobiphenyl were also present. 3. The ratio of the contents of 3- and 4-methylsulphonyl-2,2',5,5'-tetrachlorobiphenyl in the liver was 1.12 after 12 days. A lower ratio in lung and kidney indicates a high affinity of these tissues for the 4-methyl isomer.

Animals↗