摘要:

AbstractThe embryotoxic potential of diethylstilbestrol (DES) was examined in a whole embryo culture system containing a P‐450–dependent bioactivating system. Sprague‐Dawley rat embryos were explanted on day 10 and cultured for 24 hours. Concentration‐dependent effects of DES on embryonic growth parameters, viability, and embryotoxicity were observed. Concentrations of DES greater than 0.26 mM (final concentration) produced 100% embryolethality, while those below 0.15 mM were without significant effects. At a final concentration of 0.19 mM, DES produced only a slight increase in embryolethality. The same concentration elicited a marked increase in observed embryotoxicity, including prosencephalic hypoplasia, incomplete axial rotation, and open neural tubes. In addition, reductions in embryonic length, somite number, and protein and DNA content were observed. An exogenous P‐450–dependent hepatic biotransforming (catechol‐generating) system failed to alter either the incidence of observed toxic effects or measured growth parameters. Likewise, exposure of cultured embryos to 20% carbon monoxide (CO) failed to reduce DES‐induced embryotoxicity, indicating a lack of participation of an endogenous P‐450‐dependent embryonic bioactivating system. Arachidonic acid (0.20 mM) and/or indomethacin (0.50 mM) also had no observable effect on DES‐induced embryotoxicity, suggesting that prostaglandin synthase was not involved in the embryotoxic activity of DES, as has been proposed to explain its carcinogenic effect. The antioxidantsN‐acetylcysteine (1.14 mM) and α‐tocopherol (0.08 mM) failed to protect against DES‐induced embryotoxicity, while the antiestrogen tamoxifen (up to 0.85 mM) actually enhanced this effect of DES in culture. The DES analogs Z,Z‐dienestrol (DIES, 0.10 mM) and hexestrol (HES, 0.48 mM) were both embryotoxic in vitro. The presence of an exogenous P‐450‐dependent hepatic biotransforming system appeared to protect against HES‐induced embryolethality but had little effect upon DIES‐induced embryotoxicity. The results were consistent with a direct effect of DES independent of either estrogenicit

ISSN:0887-2082    

DOI:10.1002/jbt.2570020202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

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 e

ISSN:0887-2082    

DOI:10.1002/jbt.2570020203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractInhibition of mitochondrial respiratory activity and decreased lung adenosine triphosphate (ATP) concentration occur following exposure to 240 ppm·min phosgene. To determine the relationship between energy stores and the onset of phosgene‐induced pulmonary edema, we measured the ATP concentration in rapidly frozen rat lung tissue before and during pulmonary edema. Male Sprague‐Dawley rats were exposed to phosgene for four hours at concentrations of 0.05 to 1.0 ppm (12, 30, 60,120, and 240 ppm·min). Lung wet and dry weight and ATP concentration were measured immediately after exposure and for three days postexposure. The accumulation of lavage fluid protein (LFP) was also measured as an index of damage or edema due to phosgene. Lung dry weight was significantly elevated one day postexposure to 0.5 ppm phosgene, while the LFP was elevated by 0.2 ppm phosgene. Time course studies at these doses of phosgene showed that decreased ATP levels preceded the onset of edema or increase in lung weight. The ATP values expressed on a per‐lung basis showed that ATP levels were significantly lowered immediately following phosgene exposure, suggesting that the ATP changes were not the result of edema. This study is the first demonstration of a biochemical change that occurs following exposure to phosgene at a level significantly below the threshold limit value for t

ISSN:0887-2082    

DOI:10.1002/jbt.2570020204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractIn chronic or acute exposure to triethyl lead, a de novo synthesis of aminolevulinic acid dehydratase (δ‐ALAD) in bone marrow and an increased activity in circulating red blood cells can be demonstrated by activating the enzyme with dithiothreitol (DTT) and zinc. We determined the median inhibitory concentration and the apparent inhibition constant for triethyl lead on δ‐ALAD. After dosing with triethyl lead, in vivo inhibition of ALAD only occurred at the high dose, but activation analysis in vitro showed increased ALAD activity to be present at all dose levels in a dose‐dependent fashion. The use of an activation assay for red blood cell ALAD may have value as a bio‐effects monitor of exposure to org

ISSN:0887-2082    

DOI:10.1002/jbt.2570020205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractTricyclohexylhydroxytin, commonly known as Plictran® inhibited Na+, K+‐ATPase activity of rat brain synaptosomes in a concentration‐dependent manner with median inhibitory concentration (IC‐50) of 2 μM. Both K+‐stimulatedpara‐nitrophenylphosphatase and [3‐H]‐ouabain binding to synaptosomes were also inhibited by Plictran with IC‐50 values of 11 and 30 μM, respectively. Altered pH and Na+, K+‐ATPase activity curves demonstrated comparable inhibition in buffered neutral and alkaline pH ranges, and no inhibition was observed in acidic pH. The inhibition of Na+, K+‐ATPase was independent of temperature. Kinetic studies of substrate (ATP) activation of Na+, K+‐ATPase indicated uncompetitive inhibition. Results also showed noncompetitive inhibition forp‐nitrophenylphosphate and uncompetitive inhibition for K+activations ofp‐nitrophenylphosphatase. Preincubation of synaptosomes with dithiothreitol, a sulfhydryl (SH) agent, resulted in the complete protection of Plictran inhibition of Na+, K+‐ATPase, K+‐para‐nitrophenylphosphatase, and [3‐H]‐ouabain binding. The protection was specific and concentration dependent since cysteine and glutathione did not afford protection. These results indicate that Plictran inhibited Na+, K+‐ATPase by interacting with dephosphorylation of the enzyme‐phosphoryl complex and exerted a si

ISSN:0887-2082    

DOI:10.1002/jbt.2570020206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

Abstract2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) has been found to cause increases in cellular levels of pp60src, a protein tyrosine kinase in hepatocytes from the rat and guinea pig, in the thymus of the mouse in vivo and in NIH‐3T3 mouse fibroblast cell lines in vitro. Such cellular changes take place in vivo at early stages of TCDD poisoning (as early as one day after treatment in the case of mouse thymus) and at very low doses (single intraperitoneal injections of 1 μg/kg for guinea pigs, 25 μg/ kg for rats, and 30 μg/kg for mice). In addition such an effect of TCDD was observed only in a TCDD‐responsive mouse strain but not in a nonresponsive strain. This effect of TCDD is a long‐lasting one (eg, even 25 days after single dosing, the levels of pp60srcin the hepatic membrane remained high). In vitro this effect was observed in a wild‐type 3T3 cell line but was more pronounced in one of the transfected lines with a v‐srcgene, a virus‐derived oncogene known to cod

ISSN:0887-2082    

DOI:10.1002/jbt.2570020207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

ISSN:0887-2082    

DOI:10.1002/jbt.2570020201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY