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1. |
The Human Hepatic Cytochromes P450 Involved in Drug Metabolism |
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Critical Reviews in Toxicology,
Volume 22,
Issue 1,
1992,
Page 1-21
WrightonSteven A.,
StevensJeffrey C.,
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摘要:
AbstractThe cytochromes P450 are a superfamily of hemoproteins that catalyze the metabolism of a large number of xenobiotics and endobiotics. The type and amount (i.e., the animal's phenotype) of the P450s expressed by the animal, primarily in the liver, thus determine the metabolic response of the animal to a chemical challenge. A majority of the characterized P450s involved in hepatic drug metabolism have been identified in experimental animals. However, recently at least 12 human drug-metabolizing P450s have been characterized at the molecular and/or enzyme level. The characterization of these P450s has made it possible to“phenotype”microsomal samples with respect to their relative levels of the various P450s and their metabolic capabilities. The purpose of this review is to compare and contrast the human P450s involved in drug metabolism with their related forms in the rat and other experimental species.
ISSN:1040-8444
DOI:10.3109/10408449209145319
出版商:Taylor&Francis
年代:1992
数据来源: Taylor
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2. |
The Multixenobiotic Resistance Mechanism in Aquatic Organisms |
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Critical Reviews in Toxicology,
Volume 22,
Issue 1,
1992,
Page 23-43
KurelecBranko,
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摘要:
AbstractMany aquatic organisms thrive and reproduce in polluted waters. This fact indicates that they are well equipped with a defense system(s) against several toxic xenobiotics simultaneously because water pollution is typically caused by a mixture of a number of pollutants. We have found that the biochemical mechanism underlying such“multixenobiotic”resistance in freshwater and marine mussel, in several marine sponges, and in freshwater fish is similar to the mechanism of multidrug resistance (MDR) found in tumor cells that became refractory to treatment with a variety of chemotherapeutic agents. All these organisms possess a verapamil-sensitive potential to bind 2-acetylaminofluorene and vincristine onto membrane vesicles. They all express mRNA formdr1 gene, andmdr1 protein product, the glycoprotein P170. Finally, inin vivoexperiments, the accumulation of xenobiotics is enhanced in all investigated organisms in the presence of verapamil, the inhibitor of the P170 extrusion pump. The knowledge that the presence of one xenobiotic may block the pumping out, and hence accelerating accumulation, of others, may help us to understand and interprete our present and past data on different environmental parameters obtained using indicator organisms.
ISSN:1040-8444
DOI:10.3109/10408449209145320
出版商:Taylor&Francis
年代:1992
数据来源: Taylor
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3. |
Environmental Concentrations and Aquatic Toxicity Data on Diflubenzuron (Dimilin) |
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Critical Reviews in Toxicology,
Volume 22,
Issue 1,
1992,
Page 45-79
FischerSteven A.,
HallLenwood W.,
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摘要:
AbstractThe insecticide diflubenzuron (DFB) is commonly used in various mid-Atlantic states for suppression of gypsy moths in hardwood forests. DFB is potentially toxic to nontarget biota because it can enter aquatic systems through aerial application or runoff after precipitation events. Based on this concern, the objectives of this study were to: (1) compile, review, and synthesize literature on the fate, persistence, and environmental concentrations of DFB in both freshwater and saltwater environments; (2) compile, review, and synthesize acute and chronic aquatic toxicity data on DFB effects on freshwater and saltwater organisms; (3) assess possible risk to aquatic biota associated with the use of this insecticide in one specific area (Maryland); and (4) recommend future research based on the data gaps identified from this study.DFB has low solubility in water and exists as a technical grade (TG) and wettable powder (WP) formulation. The toxicity of both formulations is similar at concentrations<10μ.g/1. Organic matter is a major factor influencing the adsorption and degradation of DFB in freshwater, saltwater, and sediment. The half-life of this insecticide in freshwater is =3 days at a pH of 10 and temperature of 36°. At lower pH conditions of 6 and at the same temperature, DFB is more persistent since half-life values of≈9 days have been reported. The half-life of DFB in soil is50,000μ.g/1. Fish were also reported to accumulate DFB rapidly during acute exposures but were capable of eliminating this insecticide within 7 days. Most of the DFB aquatic toxicity studies with saltwater organisms were conducted with invertebrates. The most acutely sensitive species tested was the premolt stage of grass shrimp (96-h LC50= 1.11μ.g/1). The mummichog,Fundulus heteroclitus, the most resistant species tested, had a 96-h LC50of 32.99 mg/1. The lowest reported chronic effect concentration for saltwater organisms exposed to DFB was 0.075μ.g/1. This concentration was reported to significantly reduce reproduction in the mysid shrimp,Mysidopsis bahia.Data from the State of Maryland were used as an example for predicting the potential environmental effects of DFB on aquatic biota in Maryland waters. A case can be made for possible environmental effects given the worst case conditions of the most sensitive species (premolt stage of grass shrimp with a 96-h LC50of 1.11μ.g/1) exposed to the highest reported environmental concentration (1.5μ.g/1 DFB in water). However, in most cases, the present data base would suggest that environmental effects are not likely.
ISSN:1040-8444
DOI:10.3109/10408449209145321
出版商:Taylor&Francis
年代:1992
数据来源: Taylor
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