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Biomedical subjects

C E Mitchell

Publications and source records attributed to C E Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1985

Effect of aryl hydrocarbon hydroxylase induction on the in vivo covalent binding of 1-nitropyrene, benzo[a]pyrene, 2-aminoanthracene, and phenanthridone to mouse lung deoxyribonucleic acid.

The effect of aryl hydrocarbon hydroxylase induction on the covalent binding of 1-nitropyrene (1-NP), benzo[a]pyrene (BaP), 2-aminoanthracene (2-AA), and phenanthridone (PNDO) to mouse lung DNA was investigated. Cytochrome P-450-dependent monooxygenases were induced in mouse lung by intratracheal instillation of BaP, Aroclor-1254, or coal gas condensate (CGC) 24 hr before instillation of [3H]BaP, [3H]-2-AA, [14C]-1-NP, or [14C]PNDO. All inducing agents increased the amount of radioactivity of [3H]BaP, [3H]-2-AA, and [14C]-1-NP or metabolites bound to DNA. However, pretreatment with BaP resulted in the highest amounts of radiolabels covalently bound to DNA. At 4 hr after instillation of radiolabels in BaP-induced mice, the amounts of [3H]BaP, [3H]-2-AA, and [14C]-1-NP bound to DNA were increased 5.4-, 5.2-, and 160-fold above that of control levels; the amount of 1-NP bound to DNA was fifty times higher than the amount bound by BaP. Labeled compounds were still bound to DNA 1 week after administration. [14C]PNDO was not bound to DNA in uninduced or induced mice. Based on the amount of labeled compounds bound to DNA, pretreatment of mice with BaP and CGC induced enzymes with similar specificities; however, enzymes induced by Aroclor were less effective in the metabolism of labeled compounds to DNA-bound products. These data show that specific cytochrome P-450-dependent monooxygenases are inducible in mouse lung and suggest that pre-exposure to inducing agents may be important in the potential toxicity to proximal tissues in direct contact with inhaled xenobiotics.

Animals↗
PubMed1984

Distribution, retention, and fate of 2-aminoanthracene in rats after inhalation.

The distribution, retention, and fate of 2[3H]aminoanthracene (2-AA) were determined in male Fischer-344 rats after inhalation exposure (70 micrograms/liter; activity mass median diameter = 2.1 micron) for 30 min. Radioactivity was found in the turbinates, trachea, lungs, liver, kidneys, and gastrointestinal tract 20 min after exposure. Lower quantities of radioactivity were found in fat, brain, testes, and muscle. Inhaled 2-AA was excreted predominantly in feces (80%). The remaining 2-AA was excreted in urine. Organic soluble radioactivity was released from urinary conjugates after treatment of urine with acid and with beta-glucuronidase. This result suggests that glucuronides of both ring- and N-hydroxy-2-AA were excreted. The remaining radioactivity was water soluble and accounted for approximately one-half of the total urinary radioactivity. The organic soluble radioactivity found after hydrolysis indicated that inhaled 2-AA is extensively metabolized by rats after inhalation and excreted as conjugated metabolites. Eighty-three percent of orally administered material was absorbed into the body from the GI tract; thus, material cleared by mucociliary action after inhalation would contribute to total body burden. 2-AA, a nitrogen substituted polycyclic aromatic hydrocarbon (PAH), was very similar to other PAHs in its rapid distribution throughout the body and in its route of excretion after inhalation.

Administration, Oral↗
PubMed1984

Capitalizing on formal thought in counseling adolescents on conflicts with parents.

Parent-adolescent conflicts are frequently sufficiently severe to require third-party intervention. Because the adolescent is more likely to be in a setting where counsel is more easily available, the helping person can make use of insight and emotional maturity that is concomitant with the adolescent's acquisition of formal thought.

Adolescent↗
PubMed1983

Metabolism and macromolecular covalent binding of benzo[a]pyrene in cultured Fischer-344 rat lung type II epithelial cells.

Pulmonary biotransformation of many xenobiotics may be important for the mutagenic, carcinogenic and/or toxic response of lung tissue to these compounds. Recently, a lung epithelial cell line (designated LEC), with morphological characteristics suggestive of type II cell origin, was developed in our laboratory. When LEC cells were co-cultivated with Chinese hamster ovary (CHO) cells in a cell-mediated mutagenesis assay, LEC metabolized promutagens to metabolites mutagenic to the CHO cells [A. P. Li, A. L. Brooks, J. M. Benson and F. F. Hahn, Environ. Mutagen. 4, 407 (1982)]. In the present investigation, rates of benzo[a]pyrene (BaP) metabolism in type II lung cells were determined, and the effects of various pollutants on rates of BaP metabolism and covalent binding of BaP to LEC macromolecules were measured. Cultures of LEC cells were incubated for 24 hr with 5 microM [14C]BaP, and the culture medium was analyzed for organic- and water-soluble metabolites. LEC cells metabolized BaP to BaP-7,8-diol and BaP-9,10-diol with total rates of formation of these metabolites measured at 500-600 pmoles per 10(6) cells per 24 hr. BaP-9,10-diol was the major metabolite accounting for about 80% of the total BaP metabolized. Enzyme hydrolysis studies revealed the presence of small quantities (less than 20% of BaP metabolized) of the glucuronide conjugates of BaP-7, 8-diol and 9-hydroxy-BaP. Pretreatment of LEC cells with benz[a]anthracene, coal gas condensate, or diesel exhaust particle extract (DEP) prior to incubation with BaP resulted in a 2- to 5-fold increase in overall rates of BaP metabolism. The largest increase in covalent binding of [14C]BaP equivalents to LEC macromolecules was seen after LEC cells were pretreated with DEP (3-fold). The data suggest that lung epithelial cells may play an important role in the biological fate of inhaled xenobiotics.

Animals↗
PubMed1983

Fractionation, chemical analysis, and mutagenicity testing of low-Btu coal gasifier tar.

A tar from a low-Btu coal gasifier was subjected to parallel fractionation, chemical analysis, and bacterial mutagenicity (Salmonella) assay. Like other coal-derived tars, it was a complex mixture containing some high-molecular-weight material and several classes of organic compounds as major constituents. The results of bacterial mutagenicity testing of fractions and subfractions of the tar suggest that neutral nitrogen-containing compounds, phenols, organic bases, polycyclic aromatic hydrocarbons, and some uncharacterized high-molecular-weight materials are mutagenic to Salmonella and therefore are potentially mutagenic in higher systems.

Chemical Phenomena↗
PubMed1983

In vitro cytotoxicity to alveolar macrophages of tar from a low-Btu coal gasifier.

The cytotoxicity of fractions, subfractions, and some individual components present in tar from a low-Btu coal gasifier was determined in vitro with cultured dog alveolar macrophages. A subfraction of the tar which contained phenols and neutral nitrogen heterocycles was found to be a major contributor to the cytotoxic activity of the tar. Four compounds present in this subfraction were tested individually. Ranked from the most to the least toxic they were: 9-phenanthrol, 2-fluorenol, phenanthridone, and carbazole.

Animals↗
PubMed1983

The metabolic fate of benzo[a]pyrene in rats after inhalation.

Male Fischer-344 rats were exposed by inhalation to [3H]benzo[a]pyrene (BP) aerosols (100 micrograms/l; activity mass aerodynamic diameter, 1-2 microns) for 30 min. The concentration of organic-soluble, water-soluble and covalently-bound radioactivity was determined in rat lung, liver and kidney at 0.5, 6 and 24 h after exposure. The total amount of [3H] BP decreased rapidly in the lung as a function of time after exposure. At 0.5 h after exposure, the organic-soluble radioactivity accounted for approx. 70% of the total radioactivity in the lung. The organic-soluble radioactivity in the liver and kidney was 24% and 21%, respectively, at 0.5 h after exposure. The organic-soluble radioactivity decreased in the lung to approx. 10% of the total radioactivity by 1 day after exposure; the percent of total lung radioactivity bound to tissue at this time was 80%. Thin-layer chromatography (TLC) of extracts indicated that the organic-soluble radioactivity in the lung at 0.5 h after exposure was comprised primarily of BP, 3-OH-BP, 9-OH-BP and quinones of BP. In contrast, the organic-soluble radioactivity in the liver and kidney at 0.5 h after exposure were primarily polar metabolites, dihydrodiols, and BP. In all organs TLC profiles of the organic-soluble fraction at 6 h and 24 h after exposure were not significantly different from the 0.5 h organic soluble profiles except for the lower amount of BP.

Animals↗
PubMed1982

Distribution and retention of benzo(A)pyrene in rats after inhalation.

Tritium levels in tissues of rats were determined after inhalation of tritiated benzo(a)pyrene (3H-BaP; 500 micrograms/l; activity mass median diameter, 1-2 micrometers) for 1 h. Significant amounts of radioactivity were found in the nasal turbinates, trachea, larynx, lungs, tracheobronchial lymph nodes, kidneys, and liver immediately after exposure. Lower concentrations of radioactivity were found in the brain, testes, and spleen. Clearance of radioactivity from the respiratory tract occurred in two phases; a rapid phase where 50% of the radioactivity cleared by approx. 2 h, and a slower phase that continued for about 2 days after exposure. Radioactivity in the brain, testes, and spleen remained at about the same level during the first day after exposure and then decreased slightly during the second day. Benzo(a)pyrene inhaled in this particulate form was rapidly solubilized, translocated to internal organs, and excreted primarily in feces.

Animals↗
PubMed1981

A neuromime system for neural circuit analysis.

A system of electronic analog neurons (neuromimes) for modeling the activity in small neuronal networks is described. The system consists of sixteen analogs that simulate the integrative neuronal properties at the axon hillock and sixty-four analogs that serve to simulate synaptic interactions. The neuromime properties are based on a potential model incorporating the following properties: membrane potential, threshold, refractory period, adaptation, post-inhibitory rebound, accommodation and pacemaker potential. Use of matrix switch boards provides for convenient interconnection of the neuromime elements, allowing the construction of even complex circuits.

Animals↗
PubMed1981

Separation and characterization of the neoplastic and stromal elements of the R3230AC mammary adenocarcinoma.

The purification of the various types of cells in solid tumors is necessary for study of their biochemical and immunological functions. The R3230AC adenocarcinoma contains both a variety of stromal cells and well-differentiated neoplastic cells that possess many of the biosynthetic capabilities of normal rat mammary cells. Suspensions of cells from tumors weighing less than 1.2 g consisted of 70.4 +/- 7.2% (S.D.) malignant cells by morphology, 6.8 +/- 3.0% lymphocytes, 6.3 +/- 3.2% macrophages, 15.2 +/- 5.2% red blood cells, 0.8 +/- 0.5% granulocytes, and 0.5 +/- 0.6% unidentified cells. Sedimentation of the cells from the R3230AC tumor in a previously described isokinetic gradient resulted in a 5- to 6-fold purification of lymphocytes and macrophages. The modal fraction of malignant cells contained 95.3 +/- 2.9% malignant cells. Detection of alpha-lactalbumin by the direct peroxidase conjugate technique gave vacuolar staining of malignant cells, in contrast to the indirect and peroxidase-antiperoxidase techniques which stained ducts from normal lactating mammary gland and a wide variety of cells without vacuoles in the tumor. The best fixative for frozen sections, paraffin-embedded tissue, and cell suspensions was 50% ethanol-50% acetone. The suspensions of tumor cells contained 14.4 +/- 9.4% cells with histochemically demonstrable alpha-lactalbumin. Squamous metaplasia was commonly observed in tumors than lactating rats.

Animals↗