Linked Life Data

18402468

Source:http://linkedlifedata.com/resource/pubmed/id/18402468

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-5-22
pubmed:abstractText
Polychlorinated biphenyls (PCBs), a class of 209 individual congeners, have become persistent and ubiquitous environmental contaminants. The health impacts of PCBs, such as cancer, cardiovascular disease, developmental toxicity, and neurotoxicity, have been widely reported, but for many of these, the mechanisms of toxicity are still poorly understood. Many mechanistic studies involve cultured cells where the biological activity is dependent upon the solubility of the xenobiotic. In the present study, we investigated the factors that determine solubility as measured by diffraction spectroscopy and have modeled, with semiempirical and ab initio molecular orbital methods, the dihedral angle and calculated the dipole moment of a series of monofluorinated analogues (F-PCBs 3) of 4-chlorobiphenyl (PCB 3) as model compounds in vacuum and in water. We found a strong positive correlation between the dihedral angle, the rotation energy, the cavitation energy, the solubility, and the cytotoxicity in three human cell lines. The dipole moment was of minor influence. We also determined the influence of pH changes in a medium containing 10% fetal bovine serum (FBS), changes that could be expected when cells in culture are removed from a CO 2 incubator even for a short time. We found that the solubility is strongly affected by the pH and that this effect is not reversed by subsequent pH readjustment. In a study examining cytotoxicity, we showed that the actual pH and the pH history of a medium containing FBS were of major influence. We suggest that pH-driven changes in the tertiary and quaternary structure of albumin are responsible. These observations have implications for studies of the biological activity of semisoluble compounds, like PCBs and related compounds.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1520-5010
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1017-27
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Xenobiotic geometry and media pH determine cytotoxicity through solubility.
pubmed:affiliation
Department of Occupational and Environmental Health, University of Iowa, 100 Oakdale Campus, Iowa City, Iowa 52242-5000, USA. gregor-luthe@uiowa.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural