title: Toxicity of chemical mixtures: proteomic analysis of persisting liver and kidney protein alterations induced by repeated exposure of rats to JP-8 jet fuel vapor.
abstract: Male Sprague-Dawley rats were exposed by whole body inhalation to 1000 mg/m3 +/- 10% JP-8 jet fuel vapor or room air control conditions for 6 h/day, 5 days/week for six consecutive weeks. Following a rest period of 82 days rats were sacrificed, and liver and kidney tissues examined by proteomic methods for both total protein abundance and protein charge modification. Kidney and lung samples were solubilized and separated via large scale, high resolution two-dimensional electrophoresis (2-DE) and gel patterns scanned, digitized and processed for statistical analysis. Through the use of peptide mass fingerprinting, confirmed by sequence tag analysis, three altered proteins were identified and quantified. Numerical, but not significantly different increases were found in total abundance of lamin A (NCBI Accession No. 1346413) in the liver, and of 10-formyltetrahydrofolate dehydrogenase (10-FTHF DH, #1346044) and glutathione-S-transferase (GST; #2393724) in the kidneys of vapor-exposed subjects. Protein charge modification index (CMI) analysis indicated significant alterations (P < 0.001) in expressed lamin A and 10-FTHF DH. These persisting changes in liver and kidney proteins are discussed in terms of possible alterations in the functional capacity of exposed subjects.
authors.affiliation: Department of Biology, Indiana University--Purdue University, Columbus 47204, USA. fwitzman@iupui.edu
authors.forename: F A
authors.initials: FA
authors.lastname: Witzmann
authors.forename: R L
authors.initials: RL
authors.lastname: Carpenter
authors.forename: G D
authors.initials: GD
authors.lastname: Ritchie
authors.forename: C L
authors.initials: CL
authors.lastname: Wilson
authors.forename: A F
authors.initials: AF
authors.lastname: Nordholm
authors.forename: J
authors.initials: J
authors.lastname: Rossi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005982:Glutathione Transferase / Q000378:metabolism*; D006838:Hydrocarbons / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D034904:Lamin Type A; D034882:Lamins; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D020543:Proteome; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D006838:Hydrocarbons; C098607:JP8 aviation fuel; D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins; D020543:Proteome; D005982:Glutathione Transferase