Serum Profiling of Rat Dermal Exposure to JP-8 Fuel Reveals an Acute-Phase Response

Abstract

Dermal exposure to JP-8 petroleum jet fuel leads to toxicological responses in humans and rodents. Serum profiling is a molecular analysis of changes in the levels of serum proteins and other molecules in response to changes in physiology. This present study utilizes serum profiling approaches to examine biomolecular changes in the sera of rats exposed to dermal applications of JP-8 (jet propulsion fuel-8). Using gel electrophoresis and electrospray ionization (ESI) mass spectrometry (MS), levels of serum proteins as well as low-mass constituents were found to change after dermal exposures to JP-8. The serum protein levels altered included the acute-phase response proteins haptoglobin, ceruloplasmin, alpha(1)-inhibitor III, and apolipoprotein A-IV. Haptoglobin levels increased after a 1-day JP-8 dermal exposure and continued to increase through 7 days of exposure. Ceruloplasmin levels increased after 5 days of exposure. Serum alpha(1)-inhibitor III was reduced after a 1-day exposure and the depletion continued after 7 days of exposure. Apolipoprotein A-IV increased after a 1-day exposure and then returned to basal levels after 3- and 5-day exposures of JP-8. Levels of the acute-phase protein alpha(2)-macroglobulin were found to not vary over these time course studies. Using ESI-MS analysis directly on the sera from rats exposed to dermal JP-8, low-mass sera constituents were found to correlate with control (acetone) or JP-8 exposure.

Serum discrimination of early-stage lung cancer patients using electrospray-ionization mass spectrometry

“…The commonly used methodology for serum profiling is solid-state SELDI/MALDI-MS [5,9,11,16]. The ESI-MS approach used here and previously [10,17,19,25] has potential advantages over SELDI/MALDI-MS, including all-liquid handling, less sample manipulation/grid washings, no chemical additives, and no involvement of random crystallization processes. The lung cancer patient sera in these studies are from pathological stages I and II.…”

Discriminating patients with early-stage pancreatic cancer or chronic pancreatitis using serum electrospray mass profiling

“…Centroid area is defined as the area of the peak calculated from its geometrical m/Z center. For tandem MS/MS mass peak identifications [27], 60 m/Z ions (peak range, 700–940 m/Z, identified by LOOCV analysis for discriminating non-cancer controls from patients with stage IIB pancreatic cancer) were screened at 12 m/Z ion intervals in 10 control and 10 PDAC serum samples in the ThermoScientific ion-trap MS instrument used in the cohort discriminations. Samples were diluted 1–390 in 50% methanol, 2% formic acid, 48% water, and analyzed at a flow rate of 0.20 microliters/min.…”

“…“Hold out” databases are formed and used to validate blinded early-stage PDAC, CP, or control serum sets. Tandem MS/MS [27] is used to help identify peptides/proteins potentially involved in PDAC/control discrimination. Such straight-forward analyses, from an accessible body fluid like serum, holds promise for aiding in the diagnosis and disease monitoring and, in the future, understanding pancreatic carcino-genesis mechanisms as well as aiding in the development and analysis of therapeutic interventions for this deadly disease.…”

Mass profiling of serum to distinguish mice with pancreatic cancer induced by a transgenicKrasmutation

“…At this point in the studies, we do not know the structural identities of these peaks which are yielding the discriminations presented herein. Identification of these mass peaks, at least for the ones present in significant amounts, is a logical next step utilizing tandem mass (MS/MS) . The structural identification by tandem MS/MS of such distinguishing MS peaks will aid in understanding pancreatic carcinogenesis mechanisms in this animal model and in humans, and help in the identification of potential biomarkers and aid in future therapeutic applications.…”

“…Previously, we utilized a large number of ESI‐MS peaks to distinguish sera from early stage ovarian, lung and pancreatic cancer patients from healthy disease‐free individuals . We have also used ESI‐MS technology to distinguish sera differences in rodents infected with Listeria pathogens or xenobiotic toxicants . MS is also useful for elucidation of companion biomarkers for drug development against various cancers …”