Persistent Link:
http://hdl.handle.net/10150/282551
Title:
Correlation of pulmonary arsenic metabolism and toxicity
Author:
Barber, David Stewart, 1970-
Issue Date:
1997
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
In lung preparations, As(V) was reduced to As(III) [first order rate constant of 0.0104/min]; As(III) was oxidized to As(V) [first order rate constant of 0.005/min], methylated to MMA [K(m) = 5.383μM, V(max) = 0.00031 μmol/liter/min/mg], and complexed with GSH; MMA was converted to DMA [K(m) = 63.4 μM, V(max) = 0.0000384 μmol/liter/min/mg]; and arsine was oxidized to As(III) and As(V) and methylated. Toxicity of As(III), As(V), MMA, DMA, and arsine was assessed by measuring effects on cell and slice viability hsp32 induction, and production of DNA single strand breaks. Because all species of arsenic did not produce effects, it was possible to deduce an "active" form of arsenic from these studies. Pulmonary arsenic metabolism was modeled using SIMUSOLV. This model indicated that arsine disposition cannot be explained solely by oxidation to As(III) before methylation or further oxidation occurs. The concentration of arsenic species present in toxicity studies were predicted with this model and correlated to observed effects. There was good correlation between reduction of As(V) to As(III) with toxicity and hsp32 induction. However, the effects observed for arsine did not correlate with oxidation to arsenite.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Toxicology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Pharmacology and Toxicology
Degree Grantor:
University of Arizona
Advisor:
Carter, Dean E.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleCorrelation of pulmonary arsenic metabolism and toxicityen_US
dc.creatorBarber, David Stewart, 1970-en_US
dc.contributor.authorBarber, David Stewart, 1970-en_US
dc.date.issued1997en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractIn lung preparations, As(V) was reduced to As(III) [first order rate constant of 0.0104/min]; As(III) was oxidized to As(V) [first order rate constant of 0.005/min], methylated to MMA [K(m) = 5.383μM, V(max) = 0.00031 μmol/liter/min/mg], and complexed with GSH; MMA was converted to DMA [K(m) = 63.4 μM, V(max) = 0.0000384 μmol/liter/min/mg]; and arsine was oxidized to As(III) and As(V) and methylated. Toxicity of As(III), As(V), MMA, DMA, and arsine was assessed by measuring effects on cell and slice viability hsp32 induction, and production of DNA single strand breaks. Because all species of arsenic did not produce effects, it was possible to deduce an "active" form of arsenic from these studies. Pulmonary arsenic metabolism was modeled using SIMUSOLV. This model indicated that arsine disposition cannot be explained solely by oxidation to As(III) before methylation or further oxidation occurs. The concentration of arsenic species present in toxicity studies were predicted with this model and correlated to observed effects. There was good correlation between reduction of As(V) to As(III) with toxicity and hsp32 induction. However, the effects observed for arsine did not correlate with oxidation to arsenite.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Toxicology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorCarter, Dean E.en_US
dc.identifier.proquest9814453en_US
dc.identifier.bibrecord.b37744963en_US
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