摘要:

Studies were undertaken to test the female sex hormone β‐estradiol for its ability to modify lethality in young adult female and male mice exposed to lead acetate. Mice were injected with β‐estradiol on d —I and 0, and immediately after the second injection lead acetate was administered at four subgroup dosages ranging from 75 to 600 mg/kg body weight. Control mice were injected with only lead acetate. On d 4, 6, and 8 after Pb, the median lethal dosages (LD50s) were calculated from the observed mortality ratios by a method of moving averages. LD50 values were considerably lower for the Pb‐ and β‐estradiol‐injected groups than for the controls. Data from these experiments indicate that the β‐estradiol treatments render both female and male mice more vulnerable to the lethal effects of lead acetate.

ISSN:0098-4108    

DOI:10.1080/15287398209530168

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The influence of Zn on the acute hepatotoxicity of pyrrolizidine alkaloids (PAs) was determined in male rats. Zinc, 72 μmol/kg as ZnCI2, was administered ip for 3 consecutive days, followed 16 h after the last dose by a single ip injection of purified mixed PAs (80, 120, or 160 mg/kg) obtained from tansy ragwort (Senecio jacobaea). Hepatotoxicity of the PAs was assessed by measuring the activities of plasma glutamic‐oxaloacetic transaminase (GOT) and glutamic‐pyruvic transaminase (GPT) and by histological examination of the liver. There was a dose‐dependent increase in plasma GOT and GPT 24 h after PA administration, whereas no significant increase of these enzymes was seen after administering Zn alone. The 7‐fold increase in plasma GOT and 12‐fold increase in GPT after PA (120 mg/kg) were reduced to 2.4‐ and 2.1‐fold, respectively, by Zn pretreatment. The PA‐induced liver necrosis was either reudced in severity or abolished by Zn when the PA dose was 80 or 120 mg/kg. These results suggest a protective effect of Zn against PA hepatotoxicity. The protective effect was associated with a marked increase in liver metallothionein and a significant decrease in hepatic cytochrome P‐450 content, aminopyrine N‐demethylase activity, and in vitro microsomal conversion of the PAs to pyrroles. Liver nonprotein sulfhydryls were unchanged. The possible role of metallothionein in the sequestration of pyrrole metabolites merits further investigation.

ISSN:0098-4108    

DOI:10.1080/15287398209530169

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Eleven metals were examined for their potential to induce forward mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells. The materials tested included AICI3, CdSO4, HgCI2, K2CrO4, K2Cr2O7, MgCI2, MnCI2, NaAsO2, Na2HAsO4, NaCI, and Pb(NO3)2. Strong positive responses at survivals greater than 10% were observed with CdSO4, K2CrO4, K2Cr2O7, and MnCI2. Weak positive responses, yielding 2‐ to 3‐fold increases in mutation frequency above the solvent control at greater than 10% survival, were seen with HgCI2, NaAsO2, No2HAsO4, and Pb(NO3)2. Negative responses were obtained with MgCI2, NaCI, and AICI3.

ISSN:0098-4108    

DOI:10.1080/15287398209530170

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Acute injections of high doses of Cd induce marked testicular necrosis. However, the effects of low‐dose, oral Cd exposure on a chronic basis are not well documented. The present investigation was designed to examine the effects of such exposure as reflected in parameters of spermatotoxicity and histology. Moreover, the impact on fetal outcome was measured by evaluating teratological and postnatal neurobehavior endpoints. Male Long‐Evans hooded rats (100 d of age) were exposed to 0, 17.2, 34.4, or 68.8 ppm Cd for 70 d. During this period, the animals were maintained on a semipurified diet to control for the contributions of Zn and other trace elements. Near the end of exposure the males were mated to three female rats. One was sacrificed on d 21 of pregnancy for teratological assessment, including fetal weight, and determination of preimplantation and postimplantation loss. The other two dams were allowed to deliver, and their offspring were tested on tasks of exploratory behavior (d 21) and learning (d 90). Subsequently, the male parent was sacrificed and a variety of measures recorded including weights of testes and caudae epididymides, sperm count and sperm morphology, and Cd content of liver and kidney. One of the testes was also evaluated histologically. No significant effects were observed on any of the parameters of reproductive toxicity or fetal outcome. These findings suggest that, at the doses employed in this study, Cd did not have significant deleterious effects on the male reproductive system. Morever, the traditional view of Cd‐related testicular insult, based on acute exposure, injection protocols, needs to be reevaluated in terms of environmental relevance.

ISSN:0098-4108    

DOI:10.1080/15287398209530171

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The effects of several mono‐, di‐, and trithiols (400 μmol/kg) in mobilizing Cd from metallothionein were studied in rats 24 h after a single injection of109CdCI2(1 mg kg/Cd). BAL (2,3‐dimercaptopropanol) and propanetrithiol (1,2,3‐trimercaptopropane) were the most effective mercaptans in increasing the biliary excretion of Cd (3.1 and 5.5% of administered dose, respectively, compared to 0.04% in control injected with propylene glycol) in in situ experiments with a significant decrease in hepatic Cd. Propane‐1‐thiol was inactive and propanetrithiol was the most toxic of the compounds studied. A number of propane dithiols having sulfhydryl groups at different carbon positions with and without substituents (OH or SO−3) and dimercaptoethane were also tested for effectiveness in removing Cd. All the lipophilic compounds with two adjacent sulhydryl groups were effective in increasing the biliary excretion of Cd, but were less effective than BAL and propanetrithiol. The major form of Cd in liver cytosols of rats pretreated with CdCI2and injected with mercaptans was metallothionein. A small amount of Cd in liver cytosol and a major portion of biliary Cd in propanetrithiol‐injected rats were bound to high‐molecular‐weight proteins when fractionated on Sephadex G‐75 columns. On the other hand, after injection of BAL, most of the Cd in the bile was associated with a fraction of molecular weight 10,000. Even though Cd was present mainly as metallothionein in livers of Cd‐pretreated rats, the biliary forms of Cd after injection of BAL and propanetrithiol were different. Similar results were obtained when Cd was added in vitro to bile samples collected from control rats that were injected with these chelating agents alone. However, the Sephadex G‐75 elution profile of Cd‐BAL and Cd‐propanetrithiol after direct addition to control rat bile showed Cd complexes of identical molecular weight (<6000). These results suggested that the Cd‐binding ligands present in bile after injection of BAL and propanetrithiol were different from and had a higher molecular weight than the complexes in vitro with Cd and the respective chelating agents.

ISSN:0098-4108    

DOI:10.1080/15287398209530172

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The chromatographic properties and amino acid composition of Cd‐binding protein induced in the rat small intestine by oral administration of Cd were examined. When the intestinal mucosal cytosol from rats treated orally with Cd was chromatographed on Sephadex G‐75, Cd in the intestinal mucosa was bound 95.5% to protein of molecular weight about 10,000. A DEAE Sephadex A‐25 chromatogram of the Cd‐binding protein from Sephadex G‐75 showed two major and one minor Cd‐containing peaks as hepatic and renal metallothionein. The amino acid composition of the two major Cd peaks resembled that of metallothionein from other materials examined.

ISSN:0098-4108    

DOI:10.1080/15287398209530173

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Effects of benzene inhalation on mouse pluripotent hematopoietic stem cells have been evaluated. Male mice 8–12 wk old were exposed to 400 ppm benzene for 6 h/d, 5 d/wk, for up to 9½ wk. A t various time intervals exposed and control animals were killed, and cardiac blood was evaluated for changes in white blood cell (WBC) and red blood cell (RBC) content. In addition, femora and tibiae were evaluated for total marrow cellularity, stem cell content (as measured by the spleen colony technique), and the percent of stem cells in DNA synthesis (as determined by the tritiated thymidine cytocide technique). Exogenous spleen colonies grown from marrow of exposed animals were counted, identified, and scored by histological type. Exposure to benzene caused significant depressions of RBCs and WBCs throughout the exposure period, which continued for at least 14 d after exposure. Bone marrow cellularity and stem cell content were also depressed in exposed animals throughout the study. Tritiated thymidine cytocide of spleen colony‐forming cells was generally Increased in exposed animals, perhaps indicating a compensatory response to the reduction of circulating cells. Spleen colonies of all types were depressed after exposure to benzene. The significance of the reduction in cellularity, stem cell content, and changes in morphology of spleen colonies is discussed in relation to cellular toxicity and residual injury.

ISSN:0098-4108    

DOI:10.1080/15287398209530174

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

A commercial preparation of polybrominated biphenyls (Firemaster BP‐6) was fractionated by preferential acetone solubilization and a number of PBB congeners were purified from the resulting fractions by repeated recrystallization, alumina adsorption column chromatography, and reversed‐phase Lipidex‐500 column chromatography. The applicability of reversed‐phase Lipidex‐5000 chromatography for the separation of highly structurally similar brominated biphenyi congeners that otherwise could not be separated by alumina chromatography or recrystallization was demonstrated. In total, seven congeners were purified, including one whose structure was assigned as 2,3,4,5,3’,4 ‘‐hexabromobiphenyl.

ISSN:0098-4108    

DOI:10.1080/15287398209530175

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Isolated hepatocytes provide a suitable system for investigation of various aspects of the mechanism of a toxic response. The mechanism by which most chemicals induce hepatotoxicity is still not known. Evidence that phospholipases may play a role in cellular Injury has been reported. In the present study the effects of reported inhibitors of phospholipase A2(quinacrine, chlorpromazine, dexamethasone, and dibutyryl cyclic AMP) on diethyl maleate (DEM)‐induced lipid peroxidation, reduced glutathione (GSH) depletion, and cellular injury were examined in isolated hepatocyte suspensions. Hepatocytes were incubated for 7 h under control conditions or with (1) DEM (4 mM), (2) one of the inhibitors (qulnacrine, 10, 50, or 150 μM; chlorpromazine, 50 μM; dexamethasone, 0.1, 0.5, 1, or 2.5 mM; dibutyryl cyclic AMP, 0.1, 0.5, 1, or 2.5 mM) or aspirin (500 μM), or (3) a combination of DEM and one of the inhibitors or aspirin to determine their effect on DEM toxicity. Samples were withdrawn at hourly intervals for estimation of cellular injury (loss of intracellular K+and lactate dehydrogenase and trypan blue exclusion index), lipid peroxidation (thiobarbituric acid reactants assay), and GSH concentration. Quinacrine and chlorpromazine inhibited DEM‐induced lipid peroxidation but not cellular injury or GSH loss. This suggests that phospholipase A2may be involved in DEM‐induced lipid peroxidation but not cell damage. However, dexamethasone and dibutyryl cyclic AMP enhanced both lipid peroxidation and loss of cell viability due to DEM, suggesting novel aspects of the biochemical mechanisms of chemically induced cytotoxicity.

ISSN:0098-4108    

DOI:10.1080/15287398209530176

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Administration of parathion resulted in a greater inhibition of acetylcholinesterase (AChE) activity of plasma, erythrocytes, and brain in female rats than in male rats. No sex‐related difference was observed in the antiacetylcholinesterase activity of paraoxon, an active metabolite of parathion. Gonadectomy increased the susceptibility of males but had no perceptible effect on females, resulting in comparable inhibition of AChE by parathion in both sexes. Administration of testosterone led to recovery from increased sensitivity to the antiacetylcholinesterase activity of parathion in castrated males and afforded partial protection to ovariectomized females. On the other hand, administration of estradiol further enhanced the enzyme inhibition by parathion in castrated males but had no significant effect on that in ovariectomized females. Alterations in the status of sex hormones did not affect the antiacetylcholinesterase activity of paraoxon in plasma and erythrocytes. However, inhibition of AChE activity by paraoxon was significantly higher in brains of gonadectomized rats than those of normal rats and the effect was reversible on administration of the respective sex hormones. The results Indicate that testosterone plays an important role in determining parathion toxicity (as reflected by its antiacetylcholinesterase activity), probably by activating the oxidative cleavage of the insecticide into nontoxic metabolites.

ISSN:0098-4108    

DOI:10.1080/15287398209530177

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor