Biomonitoring of chromium(VI) deposited in pulmonary tissues: pilot studies of a magnetic resonance imaging technique in a post-mortem rodent model.
The biomonitoring of individuals exposed to chromium(VI) by inhalation is often based on determinations of chromium in body fluids such as blood, plasma or urine, or on assessments of DNA damage in non-lung surrogate tissues such as peripheral blood lymphocytes. These techniques are of some use as biomarkers of internal exposure or biological effect, mainly in the case of soluble chromium(VI) compounds, but they provide at best only indirect information about chromium(VI) concentrations in the main target organ of interest - the lung. An urgent need exists for a non-invasive technique to permit the visualization and quantification of chromium(VI) in the lung of exposed humans. This study details the development of a lung imaging technique based on the detection of paramagnetic chromium using magnetic resonance imaging (MRI). The intracellular reductive conversion of chromium(VI) is a crucial bioactivation step in its carcinogenicity, and the MRI method described here relies on the conversion of non-paramagnetic (MRI 'silent') chromium(VI) to detectable paramagnetic species such as chromium(III). Initial studies with chromium(III) revealed that a range of 2.5-5 microg chromium(III) instilled in rat lung is considered to be the lower limit of detection of this method. It was possible to demonstrate the presence of 30 microg chromium(VI) in our post-mortem rat model. The ultimate objective of this work is to determine whether this technique has applicability to the biomonitoring of chromium(VI) inhalation exposures that result in internalized lung doses in human subjects.
Shayer
Rob
R
Department of Health Tobacco Policy Team Wellington House, 133-155 Waterloo Road SE1 8UG London, UK.
Kinchesh
Paul
P
Raffray
Mark
M
Kortenkamp
Andreas
A
D000818:Animals; D015415:Biomarkers; D002857:Chromium / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D003720:Densitometry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D015415:Biomarkers; D002857:Chromium