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Induction of immunotoxicity and mixed-function oxygenase activity as biomarkers of exposure to environmental contaminants in the deer mouse (Peromyscus maniculatus)

Posted on:1996-09-15Degree:Ph.DType:Dissertation
University:Clemson UniversityCandidate:Gard, Nicholas WilliamFull Text:PDF
GTID:1464390014985653Subject:Health Sciences
Abstract/Summary:PDF Full Text Request
Immunosuppression and hepatic mixed-function oxygenase (MFO) induction were evaluated as biomarkers of exposure to polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) in deer mice (Peromyscus maniculatus). Immune function was measured by the splenic plaque-forming cell response to sheep red blood cells, and MFO induction by increases in ethoxyresorufin O-deethylase (EROD) activity. Mice were intraperitoneally dosed with 3-methylcholanthrene (3-MC), 7,12-dimethylbenz (a) anthracene (DMBA), dibenz (a,h) anthracene (DBA), benzo (b) fluoranthene (BFA), 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), 3,3{dollar}spprime,4,4spprime,5,5spprime{dollar}-hexachlorobiphenyl (PCB 169), 2,2{dollar}spprime,4,4spprime,5,5spprime{dollar}-hexachlorobiphenyl (PCB 153), Aroclor 1254, dieldrin, or arsenic. Order of immunosuppressive potency was {dollar}rm TCDD > PCB 169 > DMBA simeq DBA >{dollar} 3-MC {dollar}rm > Aroclor 1254 > dieldrin > PCB 153 simeq BFA >{dollar} arsenic. A 23-fold increase in EROD activity was caused by TCDD; a 14-fold increase by PCB 169 and 3-MC, and {dollar}<{dollar}6-fold increase by all other compounds. Immunosuppression was 3 to 330-fold more sensitive than MFO induction for detecting exposure to PAHs, and 3 to 10-fold more sensitive for exposure to PCB 153, Aroclor 1254, and dieldrin, but MFO induction was a better indicator of exposure to TCDD and PCB 169. Deer mice were estimated to be 10 to 100-fold more sensitive to immunosuppressive effects of PAHs and HAHs than strains of laboratory rodents.; Immune function and MFO induction were also measured in laboratory-reared deer mice exposed to hazardous waste site soils. In one study, soil containing 45 or 90 ppm PCB produced significant immunosuppression and EROD induction in mice after 6 days exposure. In a second study, deer mice were temporarily housed in enclosures on dieldrin-contaminated soils at the Rocky Mountain Arsenal, Colorado. Significant EROD induction occurred at the highest dieldrin concentration (20 ppm), but immune function showed no consistent concentration-response relationship, unlike results observed for mice dosed with dieldrin in laboratory trials, which suggests that soil contaminants beyond dieldrin were potentially responsible for immune responses observed at the Arsenal. Laboratory dosing trials indicated that arsenic was not likely a contributing factor.; This study found that immunosuppression and MFO induction were sensitive indicators of exposure to PAHs and HAHs in deer mice, and may be suitable biomarkers for monitoring studies at hazardous waste sites.
Keywords/Search Tags:Exposure, Induction, Deer, Biomarkers, MFO, Function, PCB, Pahs
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