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R W Teel

Publications and source records attributed to R W Teel.

At least 37 records · Page 2Linked to original sources
PubMed1987

Distribution and metabolism of ellagic acid in the mouse following intraperitoneal administration.

The distribution and metabolism of ellagic acid (EA), a naturally occurring plant phenolic compound with reported antimutagenic and anticarcinogenic activity, was investigated in mice following intraperitoneal injection. Male Swiss-Webster mice were given a single i.p. injection of [3H]EA and sacrificed at 15 min, 30 min, 60 min, 120 min and 24 h post-injection. At these times urine, blood and bile samples were obtained from each animal and various organs were removed, weighed and homogenized. Radioactivity in the samples was determined at each time interval and expressed as nmol [3H] EA/mg sample. Metabolites in urine and bile were analyzed by high-performance liquid chromatography (HPLC) and water-soluble conjugates were isolated by eluting samples of urine and bile from an alumina column. Radioactivity expressed as nmol [3H] EA/mg sample (wet weight) decreased with time in most organ homogenates. The peak radioactivity in bile appeared at 60 min post-injection while the peak radioactivity in urine occurred at 120 min. The two organs showing the highest amount of radioactivity were kidney and liver and the lowest was in brain. HPLC analysis revealed one unidentified metabolite of EA in bile and three in urine. Most of the radioactivity recovered from both bile and urine was associated with EA. Water-soluble conjugates in urine were isolated as sulfate esters, glucuronide and glutathione conjugates. Water-soluble conjugates in bile were evenly distributed as glucuronide and glutathione conjugates.

Animals↗
PubMed1987

Ellagic acid metabolism and binding to DNA in organ explant cultures of the rat.

Ellagic acid (EA) is a plant phenolic compound with postulated antimutagenic and anticarcinogenic activity. In this study, explants of esophagus, forestomach, colon, bladder, trachea, lung and liver from male Sprague-Dawley rats (130-140 g) were incubated in culture medium containing [3H]EA (20 microM, 4.5 microCi/ml) for 24 h at 37 degrees C. After extraction, purification and quantitation of explant DNA significant differences in the binding of EA to the DNA was observed. The most binding occurred in esophagus and the least in lung. Analysis of the organsoluble fraction of the culture medium by high performance liquid chromatography yielded 3 metabolites of EA. None of the metabolites were identified. Elution of water-soluble metabolites from an alumina column showed that there were sulfate ester, glucuronide and glutathione conjugates of EA in the explant culture medium from all the organs. The profile of water-soluble conjugates was very similar between colon and forestomach and between trachea and lung. These results indicate that EA binds to DNA in different tissues and that tissues metabolize EA to both organosoluble and water-soluble products.

Animals↗
PubMed1986

Ellagic acid toxicity and interaction with benzo[a]pyrene and benzo[a]pyrene 7,8-dihydrodiol in human bronchial epithelial cells.

Ellagic acid, a plant phenol present in various foods consumed by humans, has been reported to have both anti-mutagenic and anti-carcinogenic potential. To evaluate the potential anti-carcinogenic property of ellagic acid, we tested its effects on the toxicity of benzo[a]pyrene and benzo[a]pyrene, 7,8-dihydrodiol and binding of benzo[a]pyrene to DNA in cultured human bronchial epithelial cells. The toxicity of ellagic acid itself for human bronchial epithelial cells was also determined. Using a colony-forming efficiency assay, it was found that a nontoxic concentration of ellagic acid (5 micrograms/ml) enhanced the toxicity of benzo[a]pyrene 7,8-dihydrodiol in human bronchial epithelial cells. In contrast, ellagic acid at concentrations of 1.5 and 3.0 micrograms/ml inhibited binding of benzo[a]pyrene metabolites to DNA in these cells. An explanation for the potentiating effect of ellagic acid on the toxicity of benzo[a]pyrene, 7,8-dihydrodiol will require further investigation into the possible mechanisms of interaction between these two compounds.

Benzo(a)pyrene↗
PubMed1986

Ellagic acid binding to DNA as a possible mechanism for its antimutagenic and anticarcinogenic action.

Ellagic acid (EA), a plant phenol, is reported to possess antimutagenic and anticarcinogenic activity. In the present study, explants of esophagus, trachea, colon, forestomach and bladder from young male Sprague-Dawley rats were incubated in medium containing [3H]EA (4.5 mu Ci/ml) for 24 h at 37 degrees C. DNA from these explants was extracted, purified and quantitated to determine [3H]EA binding to the DNA. Significant covalent binding of [3H]EA to DNA occurred in all the explants. Calf thymus DNA incubated in 0.05 M sodium phosphate buffer containing [3H]EA covalently bound [3H]EA in a concentration dependent manner. Furthermore covalent binding of [3H]EA to calf thymus DNA was inhibited by the addition of unlabeled EA that was concentration dependent over a range of 50-150 microM and by the addition of unlabeled adenosine, cytidine, guanosine or thymidine at a concentration of 1.0 mM. These results suggest that one of the mechanisms by which EA inhibits mutagenesis and carcinogenesis is by forming adducts with DNA, thus masking binding sites to be occupied by the mutagen or carcinogen.

Animals↗
PubMed1986

Benzo(alpha)pyrene metabolism and DNA-binding in cultured explants of human bronchus and in monolayer cultures of human bronchial epithelial cells treated with ellagic acid.

Ellagic acid, a plant phenolic compound present in certain foods eaten by humans, has been reported to possess antimutagenic and anticarcinogenic properties. To evaluate the potential anticarcinogenic effect of ellagic acid in humans, we investigated the effect of nontoxic concentrations of ellagic acid on the metabolism of benzo(alpha)pyrene and binding of benzo(alpha)pyrene metabolites to DNA in cultured explants of human bronchus and in human bronchial epithelial cell cultures. Ellagic acid at concentrations of 10, 25, or 50 microM did not significantly alter the metabolism of benzo(alpha)pyrene in the bronchial explant cultures and in only one of four bronchial cell cultures. However, binding of metabolites of benzo(alpha)pyrene to DNA was inhibited in all explant and cell cultures of human bronchus by 26 to 77%. These results support the work of other investigators and suggest that ellagic acid may be an inhibitor of polycyclic aromatic hydrocarbon-induced carcinogenesis in humans.

Adult↗
PubMed1985

The effect of ellagic acid on the uptake, persistence, metabolism and DNA-binding of benzo[a]pyrene in cultured explants of strain A/J mouse lung.

Ellagic acid (EA), a plant phenol found in a variety of fruits and vegetables normally consumed by humans, inhibited the metabolism of benzo[a]pyrene (B[a]P) and covalent binding of B[a]P metabolites to DNA in cultured lung explants from strain A/J mice. Explants were incubated in medium containing EA at concentrations of 10 - 100 microM for 16 h followed by the addition of 1 microM [3H]B[a]P for 24 h. Culture medium was extracted and analyzed by high-performance liquid chromatography. DNA from the explants was extracted, purified and quantitated to determine B[a]P metabolite binding to DNA. EA at concentrations of 10, 25, 50, 100 microM inhibited the metabolism of B[a]P in lung explants by 24-47% and DNA-binding of B[a] metabolites by 36-71%. Analysis of total lipids and trichloroacetic acid insoluble fractions of homogenized lung explants showed two to three times more radioactivity in EA-treated cultures even though EA did not affect the uptake of B[a]P. Explants maintained for four days after the removal of EA and [3H]B[a]P from the culture medium exhibited significant persistence of B[a]P and B[a]P metabolites associated with the total lipid and TCA insoluble fractions and in B[a]P metabolites bound to DNA. H.p.l.c. analysis of the total lipids extracted from homogenized lung explants showed that during the first 3 days of incubation most of the radioactivity in the EA-treated cultures was unmetabolized B[a]P while that in the control cultures existed as metabolites of B[a]P. The inhibition of metabolism of B[a]P and the consistently lower B[a]P-DNA binding in EA-treated mouse lung explants support the role of EA as a naturally occurring inhibitor of B[a]P-induced carcinogenesis.

Animals↗
PubMed1985

Inhibition of benzo(a)pyrene and benzo(a)pyrene-trans-7,8-diol metabolism and DNA binding in mouse lung explants by ellagic acid.

The effect of ellagic acid, a naturally occurring plant phenol, on the binding to DNA and metabolism of benzo(a)pyrene (BP) and trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BP 7,8-DHD) in cultured explants of strain A mouse lung was investigated. The explants were cultured in a rocking organ culture chamber for 16 h in the presence or absence of 10, 25, 50, and 100 microM ellagic acid. These concentrations of ellagic acid were nontoxic as determined by biochemical and histological methods. The ellagic acid was then removed from the cultures, and the explants were incubated with either 1 microM [3H]BP or [3H]BP 7,8-DHD for 24 h. Explant DNA was isolated using hydroxylapatite chromatography, and the BP metabolites in the medium were analyzed by high-pressure liquid chromatography. Ellagic acid (50 microM) inhibited the binding of BP and BP 7,8-DHD to lung DNA by 46 to 50% and 60 to 70%, respectively. High-pressure liquid chromatography analysis showed that ellagic acid (100 microM) inhibited the metabolism of BP by 20 to 40% and of BP 7,8-DHD by 20%, as indicated by the increased amounts of unmetabolized substrates and decreased amounts of metabolites in the medium. The major BP:DNA adduct in the explants was 7R-N2-[10 beta-[7 beta, 8 beta, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl: deoxyguanosine, and its formation was reduced by 60 to 65% in the presence of 100 microM ellagic acid. These data suggest that the reduction of BP and BP 7,8-DHD metabolite binding to DNA by ellagic acid may have been due to inhibition of the formation and/or removal of BP 7,8-diol-9,10-epoxide prior to its binding to DNA.

Animals↗
PubMed1984

Selenium modified mutagenicity and metabolism of benzo[a]pyrene in an S9-dependent system.

Selenium added to the incubation mix containing rat-liver S9 modified both the metabolism and mutagenicity of benzo[a]pyrene (BaP) and several of its metabolites. Selenium (Na2SeO3) inhibited the S9-dependent mutagenic effects of BaP on Salmonella typhimurium strain TA100 as indicated by the number of histidine-dependent revertants counted. This inhibition was concentration-dependent over a range of 12.5 to 100 ppm. When used as the substrate the BaP metabolites 7,8-dihydrodiol, 9,10-dihydrodiol and 3-hydroxy also produced significantly fewer revertants in TA100 when selenium was included in the incubation mix. High-performance liquid chromatographic analysis of metabolites from S9-dependent metabolism of BaP indicated that selenium inhibited the formation of 3-hydroxy-BaP, 9,10-dihydrodiol, 7,8-dihydrodiol, 1,3- and 3,6-quinone. Eluting samples on an alumina column to isolate the conjugated metabolites showed that selenium caused 12% less binding to glucuronides, no significant differences in binding to sulfate esters or glutathione but the amount of unmetabolized BaP and unconjugated metabolites was increased by 48%. These results suggest that selenium inhibits S9-dependent BaP metabolism therefore reducing the mutagenic effects of this compound.

Animals↗
PubMed1984

A comparison of the effect of selenium on the mutagenicity and metabolism of benzo[a]pyrene in rat and hamster liver S9 activation systems.

When selenium (Na2SeO3) was included in the incubation mix containing rat or hamster liver S9 preparations both the metabolism and mutagenicity of benzo[a]pyrene (BaP) and several of its metabolites were altered. At non-toxic concentrations selenium inhibited the S9 dependent mutagenicity of BaP and a number of its metabolites on Salmonella typhimurium strain TA100 as indicated by the number of histidine independent revertants observed. High performance liquid chromatographic analysis of S9 generated metabolites of BaP from rat and hamster liver indicated that selenium caused quantitative differences in the amounts of the metabolic products. In hamster liver S9 differences were reflected in decreased amounts of strongly mutagenic BaP-7,8-dihydrodiol and increased amounts of 4,5- and 9,10-dihydrodiols that were weakly mutagenic to TA100 in that system. In rat liver S9 selenium caused quantitatively similar decreases in BaP-7,8- and 9,10-dihydrodiol and 3-hydroxy-BaP. When used as substrate 3-hydroxy-BaP was the most mutagenic to TA100 in the rat activation system whereas BaP-7,8-dihydrodiol was most mutagenic in the hamster S9 system. Assays that measured the formation of water-soluble conjugates of BaP indicated that selenium did not significantly alter the formation of sulfate ester or glutathione conjugates although a 12-17% reduction of labeled metabolites bound to the glucuronide fraction was observed. Results described in this report suggest that selenium modified the metabolism and hence the mutagenicity of BaP to TA100 by affecting mixed-function oxidase and/or epoxide hydratase activity in both the rat and hamster liver S9 activation systems.

Animals↗
PubMed1979

Induction of aryl hydrocarbon hydroxylase in primary cultures of type II alveolar lung cells and binding of metabolically activated benzo[a]pyrene to nuclear macromolecules.

Alveolar-like structures cultured on a gelatin sponge substrate are composed of cells resembling type II alveolar pneumonocytes. These cells contain aryl hydrocarbon hydroxylase (AHH) as determined by fluorescent measurements of water-soluble product from the metabolism of polycyclic aromatic hydrocarbons (PAH). Of 3 compounds tested, benzo[a]pyrene (BP) stimulates the highest level of AHH activity. Activity reaches a peak in 6 day cultures and remains relatively stable for a culture period of 12 days. Metabolites of tritium labeled BP interact with nuclear macromolecules in these cells as determined by measurements of 3H binding to DNA, histone and non-histone chromosomal proteins. A preferential binding to the non-histone protein fraction occurs.

Animals↗
PubMed1976

The formation of histotypic structures from monodisperse fetal rat lung cells cultured on a three-dimensional substrate.

Enzymatically dissociated lungs from rat fetuses at 19-days gestation yield single cells which reaggregate to form alveolar-like structures when cultured on gelatin sponge discs. These structures form within 2 days and have been maintained in vitro for as long as 6 weeks. They are composed primarily of type II pneumonocytes as characterized by large, lightly stained nuclei and cytoplasmic inclusion bodies. The lamellar structure of these inclusion bodies has been confirmed by electron microscopy. The dynamic formation of inclusion bodies is suggested by the presence of lamellar bodies in the extra-cellular space and the appearance of new inclusions in the cytoplasm of the type II pneumonocytes. The formation and long-term maintenance of histotypic lung structures in vitro provides a model system for the study of lung development and synthesis of surfactant by type II alveolar pneumonocytes.

Cells, Cultured↗
PubMed1976

An organotypic in vitro model system for studying pulmonary surfactant production by type II alveolar pneumonocytes.

This report describes an in vitro model system in which monodisperse fetal rat lung cells reorganize to form alveolar-like structures when cultured on a gelatin sponge matrix. The alveolar-like structures are composed of cells that have morphologic characteristics like those of the type II alveolar pneumonocytes of intact lung. These morphologic characteristics include lightly stained nuclei, microvilli on the apical surface, and osmiophilic lamellar bodies in the cytoplasm. The presence of osmiophilic lamellar bodies and tubular myelin in the lumen of the alveolar-like structures suggests that the cells in these structures are producing pulmonary surfactant. The formation and long-term maintenance of these alveolar-like structures provide a unique in vitro model system for studies of the synthesis, storage, and secretion of pulmonary surfactant.

Animals↗
PubMedDate not supplied

Lack of the inhibitory effect of intragastrically administered capsaicin on NNK-induced lung tumor formation in the A.J mouse.

Capsaicin is the principal component in Capsicum fruits consumed by humans worldwide as a food additive. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is thought to be an important causative factor in human lung cancer. Dietary factors are reported to modify lung tumor formation in laboratory animals and in humans. In this study, NNK-induced lung tumor formation in female A/J mice given intragastric doses of capsaicin (5 mg/kg body wt) was compared to mice not receiving capsaicin. At the end of the 21 week study, mice treated with capsaicin had an average of 17.1 +/- 1.8 lung tumors/mouse while untreated mice had 19.6 +/- 2. There were 100% lung tumor bearers in each group. Capsaicin alone did not affect spontaneous formation of lung tumors. Our results do not support a possible chemoprotective effect of dietary capsaicin toward NNK-induced lung tumors in human smokers.

Adenoma↗
PubMedDate not supplied

Effects of intragastrically administered Pycnogenol on NNK metabolism in F344 rats.

NNK is a tobacco-specific nitrosamine that requires metabolic activation by cytochrome P450 enzymes. NNK may be metabolized via carbonyl reduction, N-oxidation, and alpha-carbon hydroxylation. Pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark and is available as a dietary supplement. We have previously shown that Pycnogenol inhibits the in vitro metabolism of NNK in lung and liver microsomes of F344 rats in a concentration-dependent manner. In this report, intragastrically administered Pycnogenol in saline affected NNK metabolism in lung microsomes differently than in liver microsomes of F344 rats. The administered Pycnogenol was inhibitory toward NNK activation in lung microsomes but not in liver microsomes suggesting that Pycnogenol may afford chemoprotection toward NNK-induced lung tumorigenesis when administered orally but not toward NNK-induced liver tumorigenesis. The effects of intragastrically administered Pycnogenol on NNK metabolism in lung and liver microsomes were similar in 6 mo and 20 mo old rats although the level of NNK metabolism was less in the 20 mo old animals.

Administration, Oral↗