bluuebunny/crossref_metadata_2025_split huggingface dataset:
The murine aromatic hydrocarbon responsiveness locus: A comparison of receptor levels and several inducible enzyme activities among recombinant inbred lines
Authors: Bigelow Sanford W. , Nebert Daniel W. 
Published: October 2006

AbstractThe aromatic hydrocarbon responsiveness (Ah) locus has been correlated with genetic differences in the risk of drug toxicity, teratogenesis, chemical carcinogenesis, and mutagenesis. Hepatic cytosolic Ah receptor levels, 2‐amino‐5‐chlorobenzoxazole (zoxazolamine) paralysis time following β‐naphthoflavone treatment and aryl hydrocarbon hydroxylase (AHH),3 acetanilide 4‐hydroxylase (Ac4H), and NAD(P)H:menadione oxidoreductase (NMOR);4 induction by 3‐methylcholanthrene were studied in (a) the progenitors C57BL/6J (Ahb/Ahb) and DBA/2J (Ahd/Ahd) and 25 BXD recombinant inbred lines, (b) the progenitors C57BL/6N and C3H/HeN and 14 B6NXC3N recombinant inbred lines, and (c) the progenitors C57BL/6J and C3H/HeJ and 12 BXH recombinant inbred lines. The Ahb phenotype exhibits >5 femtomole receptor/mg of cytosolic protein, ≤15 minutes zoxaxolamine paralysis time, and twofold to 15‐fold induction of these three hepatic enzyme activities; the Ahd phenotype exhibits ≤2 fmol receptor/mg protein, >15 minutes zoxazolamine paralysis time, and <30% induction of these three activities. Among the BXD lines but especially among the B6NXC3N and BXH lines, high frequencies of recombination were found; the phenotype of each of the five parameters did not segregate with the phenotype of each of the other parameters in four or more recombinant lines. This report shows for the first time that AHH induction by 3‐methylcholanthrene can occur in the Ahd phenotype mouse. These data underline the complexity of this genetic system when genes from C57BL/6 and DBA/2 are combined and particularly when genes from C57BL/6 and C3H/He inbred mouse strains are combined.
Ca2+ homeostasis and cytotoxicity in isolated hepatocytes: Studies with extracellular adenosine 5′‐triphosphate
Authors: Mirabelli Francesca , Bellomo Giorgio , Nicotera Pierluigi , Moore Margo , Orrenius Sten 
Published: October 2006

AbstractThe incubation of isolated rat hepatocytes with extracellular adenosine 5′‐trihosphate (ATP) resulted in an inhibition of Ca2+ efflux. The ATP‐induced Ca2+ accumulation as determined by the increase in phosphorylase a activity and the Ca2+ ‐sensitive fluorescent indicator (2‐[(2‐bis‐[carboxymethyl]‐amino‐5‐methylphenoxy)‐methyl]‐6‐methoxy‐8‐bis‐[carboxymethyl] aminoquinoline‐tetrakis‐[acetoxymethyl]ester) (Quin 2‐AM) was associated with both the hydrolysis of ATP and the phosphorylation of a 110 kDa protein. No significant alteration in the intracellular ATP level was observed.The appearance of surface blebs and cytotoxicity followed the rise in cytosolic Ca2+, suggesting that the increased free Ca2+ may be responsible for the loss of viability. When a calmodulin inhibitor, 1‐[bis(4‐chlorophenyl)methyl]‐3‐[2‐(2,4‐dichlorophenyl)‐2‐[(2,4‐dichlorophenyl)methoxy] ethyl]‐1H‐imidazolium chloride (calmidazolium), was included in the medium prior to ATP addition, bleb formation was reduced and the loss of viability was completely prevented, indicating that a Ca2+ ‐calmodulin process may be involved in the initiation of cytotoxicity.
The effects of nonadecafluoro‐n‐decanoic acid on serum retinol and hepatic retinyl palmitate hydrolase activity in male sprague‐dawley rats
Authors: Powers Robert H. , Aust Steven D. 
Published: October 2006

AbstractThe effects of nonadecafluoro‐n‐decanoic acid (NDFDA) on serum retinol levels and hepatic retinyl palmitate hydrolase (RPH) activity were investigated in male Sprague‐Dawley rats given a single intraperitoneal (IP) dose of 0, 50, or 100 mg/kg NDFDA and sacrificed at two, eight, or 11 days. Treated animals exhibited depressed serum retinol levels, lymphoid involution, and failure to gain weight in proportion to the dose. Hepatic RPH activities were depressed in both treatment groups at all time points and correlated with serum retinol levels. Hepatic retinol levels were also depressed by Day 11. Extraction of hepatic homogenates with acetone removed NDFDA and increased RPH activities twofold and threefold for the low‐ and high‐dose groups, respectively. Analysis of partially purified RPH showed both NDFDA and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) to be noncompetitive inhibitors: K1 = 450 and 750 μM, respectively. We conclude that NDFDA causes a decrease in the mobilization of vitamin A from the liver by noncompetitive inhibition of RPH.
Synthesis and genotoxicity of acetoxyoxirane, the epoxide of vinyl acetate
Authors: Simon P. , Epe B. , Mützel P. , Schiffmann D. , Wild D. , Ottenwälder H. , Fedtke N. , Bolt H. M. , Henschler D. 
Published: October 2006

AbstractAcetoxyoxirane, the epoxide of vinyl acetate and a potential reactive intermediate, was synthesized and characterized by 13C‐nuclear magnetic resonance (13C‐NMR) and mass spectroscopy. The compound induced lesions (endonuclease‐sensitive and alkali‐labile sites) in supercoiled PM2 DNA in vitro and was directly mutagenic toward Salmonella typhimurium TA100. The mutagenicity of the epoxide in phosphate buffer (pH 7.4, 37 °C) decreased, with an initial half‐life of 2.8 minutes, and mutagenicity was completely abolished by addition of S‐9 mix. Acetoxyoxirane did not induce unscheduled DNA synthesis on incubation with Syrian hamster embryo fibroblasts (SHE cells). These findings may possibly be explained by an effective inactivation of acetoxyoxirane by esterases when these are present in the biological system. This view is consistent with the lack of acetoxyoxirane detected in rat liver microsomal incubations of vinyl acetate.
Identification of S‐1,2,2‐trichlorovinyl‐N‐acetylcysteine as a urinary metabolite of tetrachloroethylene: Bioactivation through glutathione conjugation as a possible explanation of its nephrocarcinogenicity
Authors: Dekant Wolfgang , Metzler Manfred , Henschler Dietrich 
Published: October 2006

AbstractThe elimination and metabolism of [14‐C]‐tetrachloroethylene (Tetra) was studied in female rats and mice after the oral administration of 800 mg/kg [14‐C]‐Tetra. Elimination of unchanged Tetra was the main pathway of elimination in both species and amounted to 91.2% of the dose in rats and 85.1% in mice. [14‐C]‐Carbon dioxide (CO2) was found to be a trace metabolite of [14‐C]‐Tetra. Only a small part of the applied dose was transformed to urinary (rats = 2.3%, mice = 7.1%) and fecal (rats = 2.0%, mice = 0.5%) metabolites. The urinary metabolites were separated and quantified by high performance liquid chromatography (HPLC) and identified by gas liquid chromatography/mass spectrometry (GC/MS). The following metabolites could be identified: oxalic acid (8.0% of urinary radioactivity in rats, 2.9% in mice), dichloroacetic acid (5.1%, 4.4%), trichloroacetic acid (54.0%, 57.8%), N‐trichloroacetyl‐aminoethanol (5.4%, 5.7%), trichloroethanol, free and conjugated (8.7%, 8.0%), S‐1,2,2‐trichlorovinyl‐N‐acetylcysteine (N‐acetyl TCVC) (1.6%, 0.5%), and another conjugate of trichloroacetic acid (1.8%, 1.3%). The structures of the identified metabolites indicate two different pathways operative in Tetra biotransformation: cytochrome P‐450‐mediated epoxidation forming reactive metabolites in the liver and conjugation of Tetra with glutathione (GSH) catalyzed by glutathione transferase(s). The formation of reactive intermediates by renal processing of the glutathione conjugates may provide a molecular mechanism for the nephrotoxicity and nephrocarcinogenicity of Tetra in male rats.
Regulation of hepatic malic enzyme by perfluorodecanoic acid
Authors: Kelling Christopher K. , van Rafelghemp Marc J. , Drake Richard L. , Menahan Lawrence A. , Peterson Richard E. 
Published: October 2006

AbstractPerfluorodecanoic acid (PFDA) administration to adult male rats increased both the activity of hepatic malic enzyme and liver weight in a dose‐dependent manner. Hepatomegaly and augmented activity of malic enzyme in liver were apparent within one day following PFDA administration and reached a plateau by three days posttreatment. Malic enzyme quantity per liver in PFDA‐treated rats was elevated within one day following dosing and increased continually throughout five days posttreatment. Administration of PFDA to rats in the fed state also led to an increase in the specific activity of hepatic malic enzyme that peaked at three days following dosing. When compared to the fed condition, rats fasted for 48 hours had a decrease in both relative liver weight and the quantity of supernatant protein per liver. The total activity (U/liver) and specific activity of malic enzyme in the liver were also reduced in the fasted state. During the 24 hours after treatment in rats fasted for 48 hours, the body weight as well as the absolute and relative liver weight of animals receiving vehicle declined continuously in the absence of feed. Following the administration of PFDA to fasted rats, body weight was maintained until eight hours posttreatment but then declined at a rate similar to that found with the vehicle‐treated group. Absolute and relative liver weight in PFDA‐treated rats were increased significantly at eight hours posttreatment when compared to those receiving vehicle, and this increment was maintained throughout the rest of the 24 hours following dosing. While the activity and enzyme content of hepatic malic enzyme decreased in the vehicle‐treated group, administration of PFDA to rats fasted for 48 hours prevented their decline. The specific activity of hepatic malic enzyme in 48 hours fasted rats receiving PFDA was also elevated significantly at 16 hours posttreatment. Thus, the administration of PFDA to the adult male rat in both the fed and fasted nutritional states was found to regulate hepatic malic enzyme by not only increasing enzyme quantity but also by augmenting the specific activity, (ie, catalytic state) of the enzyme.
2,3,7,8‐tetrachlorodibenzo‐p‐ dioxin reduces high‐affinity binding of epidermal growth factor to cell surface receptors in C3H 10T1/2 cells
Authors: Moriya Masaaki , Matsumura Fumio , Kalimi Ghulm H. 
Published: October 2006

AbstractThe effect of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) on epidermal growth factor (EGF)‐binding characteristics was studied in a cultured embryonic fibroblast cell line, C3H 10T1/2. At very low concentrations, TCDD was found to cause a persistent decline in EFG binding, the median effective concentration (EC‐50) being 10−12M. This particular effect was most conspicuous when TCDD was added at the time of medium change with fresh Dulbecco's modified Eagle's medium. Cells at an early stage of confluency were more responsive to TCDD than those at a later stage. Although most reported TCDD‐evoked biological changes are recognized to occur slowly during the course of a few days to weeks, the response of C3H 10T1/2 cells to TCDD was swift, showing a sign of decline of EGF binding as early as three hours after TCDD addition. C3H 10T1/2 cells appear to be an excellent in vitro model to study TCDD's biochemical action mechanisms.
Effect of nickel(II) on DNA‐protein binding, thymidine incorporation, and sedimentation pattern of chromatin fractions from intact mammalian cells
Authors: Patierno Steven R. , Sugiyama Masayasu , Costa Max 
Published: October 2006

AbstractNuclear uptake and chromatin binding of nickel(II) was investigated in Chinese hamster ovary (CHO) cells. The cytoplasmic:nuclear ratio of nickel immediately following treatment was 5:1, but by 24 and 48 hours this ratio decreased to 4:l and 2:1, respectively, indicating that nickel is retained longer in the nucleus than cytoplasmic nickel. Chromatin was fractionated by sonication and centrifugation into fast‐sedimenting, magnesium‐insoluble, or magnesiumsoluble components. The magnesium‐insoluble portion bound more nickel ions and retained the metal longer than either the magnesium‐soluble or the fastsedimenting fractions. Treatment of cells with nickel chloride (NiCl2) decreased the amount of DNA in the magnesium‐insoluble fraction but increased the amount of DNA in the fast‐ sedimenting chromatin fraction. The magnesium‐insoluble fraction isolated from nickel‐treated cells contained approximately ten times more [35‐S]‐methionine–labeled protein per milligram DNA compared with untreated cells. The magnesium‐soluble and the fast‐sedimenting fractions isolated from the nickel‐treated cells did not exhibit a similar increase in [35‐S]‐methionine–labeled protein per milligram of DNA. Nickel treatment suppressed [14‐C]‐thymidine incorporation into total DNA by 30% compared with untreated cells. However, the magnesium‐insoluble chromatin fraction from nickel‐treated cells had a tenfold to 20‐fold increase in thymidine incorporation, while the other chromatin fractions did not exhibit an increase in thymidine incorporation. These findings indicate that nickel induced widespread alterations in chromatin conformation and preferentially interacted with an Mg‐insoluble component of chromatin.
Characterization of cadmium‐binding proteins detected in rat liver by the western blotting technique
Authors: Aoki Yasunobu , Suzuki Kazuo T. 
Published: October 2006

AbstractOut of the three cadmium‐binding proteins (CD‐BPs) in rat liver parenchyma (40K, 29K, and 24K CdBPs), the 40K Cd‐BP showed the highest affinity for cadmium (Cd), with a dissociation constant (KD) of 1.2 × 10−8M. This is in between the affinity of human serum albumin KD = 3.8 × 10−5M) and metallothionein (KD = < 10−11). These Cd‐BPs may be responsible for hepatic sequestration of cadmium.
Alterations in platelet aggregation and microsomal benzo‐α‐pyrene hydroxylase activities after exposure of rats to a prudhoe bay crude oil
Authors: Chaudhury Shibani , Martin Marie , Payne Jeremiah F. , Rahimtula Anver 
Published: October 2006

AbstractAdministration of a Prudhoe Bay crude oil (PBCO) to rats has been shown to (a) inhibit platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid, or epinephrine and (b) induce benzo‐α‐pyrene hydroxylase (BPH) in the liver and small intestine. Maximum inhibition of aggregation (90%) was seen 12 to 16 hours subsequent to dosing. However, substantial inhibition was observed as early as four hours and as late as 48 hours after dosing. Of particular interest was the sensitivity of the platelet response compared with the putatively sensitive response of monooxygenase induction in liver. As little as 0.1 ml of PBCO per kilogram body weight (bw) caused an inhibition of aggregation with all three agonists. A similar inhibition of the release of ADP from platelets in the presence of arachidonic acid or epinephrine was also observed. In contrast, hepatic BPH activity showed only a modest increase (67%) over the control value even after administration of 2 ml of PBCO per kilogram body weight. Small intestine BPH activity was more sensitive, showing a gradual increase of up to 19‐fold 24 hours after dosing with 2 ml of PBCO per kilogram body weight. The sensitivity of the platelet response is of general environmental interest and evaluating platelet aggregation in humans may be important as a noninvasive assay for exposure to either accidental or “acceptable” levels of petroleum hydrocarbons in the occupational environment.
Gentamicin‐induced alterations in phospholipid metabolism in cultured human proximal tubular cells
Authors: Chatterjee Subroto 
Published: October 2006

AbstractThe effects of gentamicin on phospholipid levels and metabolism and the uptake of phosphatidylcholine (PC) adsorbed to low‐density lipoprotein (LDL) were investigated in cultured human proximal tubular (PT) cells. Cells incubated with gentamicin (0.3 mM) for one to 21 days had a similar increase in the cell number and protein as compared to control cells. However, the cellular levels of phosphatidylcholine (PC) and sphingomyelin (SM), but not other phospholipids, increased in a time‐dependent manner. Incubation of gentamicin (0.3 to 3.0 mM) resulted in a concentration‐dependent increase in the cellular levels of PC (50% to 320%) and SM (20% to 40%).Gentamicin stimulated the incorporation of [14C]‐acetate into diacylglycerol, PC, and SM in the order of 300%, 66%, and 20%, respectively, but not into lysophosphatidylcholine (LPC). Similarly, gentamicin stimulated the incorporation of [14C]‐choline into PC and SM in the order of 300% and 172%, respectively, but not into LPC as compared to control cells. In addition, gentamicin also stimulated the incorporation of [14C]‐choline into cytidine diphosphocholine (CDP‐choline). However, the endocytosis of [14C]‐PC‐LDL was lower in cells incubated with gentamicin than in control cells. Thus, exogenously derived PC on LDL does not contribute to the increased cellular levels of PC in PT cells incubated with gentamicin.The activity of cytidine triphosphate (CTP):phosphocholine cytidyltransferase was moderately lower in cells incubated with gentamicin as compared to control. By contrast, the activity of phospholipase A1 and phospholipase C was twofold lower in cells incubated with gentamicin for 21 days as compared to control. Thus, increased incorporation of [14C]‐acetate and [14C]‐choline into PC in cells incubated with gentamicin may not only be due to increased endogenous synthesis but to decreased catabolism of newly synthesized PC. We conclude that gentamicin impairs the lysosomal catabolism of PC, leading to its accumulation in PT cells. This phenomenon may be an indication of gentamicin‐induced nephrotoxicity in man.
Attenuation of 2‐methoxyethanol and methoxyacetic acid‐induced digit malformations in mice by simple physiological compounds: Implications for the role of further metabolism of methoxyacetic acid in developmental toxicity
Authors: Welsch F. , Sleet R. B. , Greene J. A. 
Published: October 2006

AbstractThe ethylene glycol ether 2‐methoxyethanol (ME) and its oxidation product methoxyacetic acid (MAA) are selective embryotoxins and equipotent as inducers of digit malformations when given by gavage to pregnant CrI:CD‐1 ICR BR mice on gestation day 11. Earlier observations showed that the teratogenic effects were attenuated by delayed administrations of ethanol given at a time when all ME is already converted to MAA. That outcome suggested that acetate from ethanol catabolism might compete with methoxyacetate in biosynthetic reactions relevant to MAA‐induced malformations. Furthermore, 14C derived from [1,2‐14C]‐ME or [1‐14C]‐MAA is incorporated into all marcromolecular fractions of the embryo, and 14C is exhaled by the dam in 14CO2. Those data indicate that 14C derived from 14C‐ME catabolism enters into many metabolic reactions. The present study examined acetate and other simple physiological compounds with close relationships to carbon and one‐carbon moiety metabolic pathways for their ability to attenuate digit malformations upon concomitant dosing with ME. All of the agents examined reduced the teratogenic effect significantly with a potency rank order of formate ≫ acetate = glycine ≫ D‐glucose. The common link for their efficacy may be the one‐carbon moiety oxidation pathway that involves tetrahydrofolic acid as a catalyst of one‐carbon transfer into purines and thymidylate. Carbon from all of the attenuators administered is incorporated into those bases and then into DNA. It appears as if methoxyacetate enters into biochemical reactions analogous to those of acetate. This speculation is supported by the metabolic fate of 14C from 14C‐ME in dam and embryo. Based on the indirect evidence obtained with all of the simple compounds that attenuate the ME‐induced digit malformations, we postulate that abnormal macromolecules are generated by anabolic reactions and that those products disrupt normal paw development.
Age and growth‐related changes in cyclopiazonic acid‐potentiated lipophilic cation accumulation by cultured cells and binding to freeze‐thaw lysed cells
Authors: Riley Ronald T. , Goeger Douglas E. , Norred William P. , Cole Richard J. , Dorner Joe W. 
Published: October 2006

AbstractIn a previous study (1) we demonstrated that increased tetraphenylphosphonium (TPP) uptake by renal epithelial cells (LLC‐PK1) exposed to the fungal metabolite cyclopiazonic acid (CPA) was not a result of hyperpolarization across the plasma membrane even though CPA‐potentiated TPP uptake could be totally inhibited by the depolarizing agent carbonylcyanide‐m‐chlorophenylhydrazone (CCCP). We now demonstrate that CPA potentiates TPP accumulation by proliferating skeletal muscle (L6) and LLC‐PK1 cells but not by nonproliferating primary rat hepatocytes. In LLC‐PK1 cells, CPA‐potentiated TPP accumulation is observed in cells at all ages. In s cells, CPA‐potentiated TPP accumulation is maximal soon after subculturing, and as the cells age they become less sensitive to CPA until TPP accumulation by CPA‐treated cells approaches that of untreated cells. The temporal change in sensitivity of L6 cells to CPA may be related to biochemical and/or metabolic changes which occur as the cells age in culture. Hepatocytes, LLC‐PK1 cells, and L6 cells permeabilized by freeze‐thaw lysis, all exhibit CPA‐potentiated TPP partitioning, even in the presence of CCCP. This result indicates that both TPP and CPA must have access to the intracellular space in order for potentiated TPP partitioning to be observed. We hypothesize that the site of interaction between CPA and TPP is intracellular and probably associated with the cytoplasmic side of the plasma membrane and possibly the mitochondria.
Cerebral glucose and glycogen metabolism in diazinon‐treated animals
Authors: Matin M. A. , Husain K. 
Published: October 2006

AbstractThe intraperitoneal (IP) treatment of rats with diazinon (40 mg/kg) resulted in a variety of changes in the brain. Glycogen was depleted, but there was an increase in the activities of glycogen phosphorylase, phosphoglucomutase, hexokinase, lactate dehydrogenase, and fructose 1,6 diphosphatase. The activity of glucose‐6‐phosphatase was unaffected while that of cholinesterase was significantly reduced. Lactic acid content was increased, while that of pyruvate was not altered. Animals developed tremors and convulsions, which were maximal two hours after treatment. The induced changes may be compensatory mechanisms to provide extra energy to cerebral tissue as a result of the stimulatory effects in diazinon‐treated animals.