Linked Life Data

15178806

Source:http://linkedlifedata.com/resource/pubmed/id/15178806

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-8-12
pubmed:abstractText
Quinones are believed to induce their toxicity by two main mechanisms: oxygen activation by redox cycling and alkylation of essential macromolecules. The physicochemical parameters that underlie this activity have not been elucidated, although redox potential is believed to play a significant role. In this study, we have evaluated the cytotoxicity, formation of reactive oxygen species (ROS), and the glutathione (GSH) depleting ability of 14 p-benzoquinone congeners in primary rat hepatocyte and PC12 cell cultures. All experiments were performed under identical conditions (37 degrees C, 5% CO2/air) in 96-well plates. The most cytotoxic quinone was found to be tetrachloro-p-benzoquinone (chloranil), and the least toxic was duroquinone or 2,6-di-tert-butyl-p-benzoquinone. The cytotoxic order varied between the cell types, and in particular, the di-substituted methoxy or methyl p-benzoquinones were particularly more cytotoxic towards PC12 cells. We have derived one- and two-parameter quantitative structure-toxicity relationships (QSTRs) which revealed that the most cytotoxic quinones had the highest electron affinity and the smallest volume. Cytotoxicity did not correlate with the lipophilicity of the quinone. Furthermore, we found that p-benzoquinone cytotoxicity correlated well with hepatocyte ROS formation and GSH depletion, whereas in PC12 cells, cytotoxicity did not correlate with ROS formation and somewhat correlated with GSH depletion. Hepatocytes had far greater hydrogen peroxide detoxifying capacity than PC12 cells, but PC12 cells contained more GSH/mg protein. Thus, p-benzoquinone-induced ROS formation was greater towards PC12 cells than with hepatocytes. To our knowledge, this is the first QSTR derived for p-benzoquinone cytotoxicity in these cell types and could form the basis for distinguishing certain cell-specific cytotoxic mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
148-59
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Application of quantitative structure-toxicity relationships for the comparison of the cytotoxicity of 14 p-benzoquinone congeners in primary cultured rat hepatocytes versus PC12 cells.
pubmed:affiliation
Leslie Dan Faculty of Pharmacy, University of Toronto, ON, Canada M5S 2S2.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't