Biomonitoring of Air Pollution Exposure and Pathological ...
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Biomonitoring of Air Pollution Exposure and
Pathological Changes in Individuals
Junfeng (Jim) Zhang, PhD
Professor of Global and Environmental Health
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Highlights
Exposure Biomarker for diesel nitro-PAHsUrine (CEF published work)
Urine (HEART study)
Hb-adducts of BaP and nitro-PAHs
Biomarkers of physiological response/pathway
MDA
8-OHdG
nitrite
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Exposure Biomarker for diesel nitro-PAHs
Urine
Diesel exhaust (DE) is a significant source of air
pollution that has been linked to respiratory and
cardiovascular morbidity and mortality.
Nitro-PAHs have been detected from diesel
exhaust particles, and appear to be a more specific
marker of DE exposure.
Nitro-PAHs, once inhaled, can be partially
metabolized to the corresponding amino-PAHs
and excreted in urine.
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Nitroreductase
cytochrome P-450
+
Hydrolysis Hydrolysis
Hemoglobin adducts DNA adducts
1-Nitro-Pyrene 1-Amino-Pyrene
1-Nitroso-Pyrene
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Exposure Biomarker for diesel nitro-PAHs
CEF study
• An HPLC-fluorescence system was used to
analyze 1-aminopyrene in human urine
samples collected prior to and during 24 h
following the start of 1 h controlled
exposure to DE (target concentration 300
µg/m3 as PM10) and clean air control.
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Exposure Biomarker for diesel nitro-PAHs
Beijing Olympic study
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1&2-amino-naphthalene
-40
-20
0
20
40
60
0 1 2 3
Total PAHs
0 1 2 3
B[a]P
0 1 2 3
pyrene
0 1 2 3
EC
0 1 2 3
PN
0 1 2 3
PM2.5
0 1 2 3
O3
0 1 2 3
NO2
Perc
ent changes in 1
&2-A
N
per
IQR
incre
ases in p
ollu
tants
Pollutant * Lag
0 1 2 3
CO
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1-amino-pyrene
-40
-20
0
20
40
60
80
Perc
ent changes in 1
-AP
per
IQR
incre
ases in p
ollu
tants
Pollutant * Lag
0 1 2 3
CO
0 1 2 3
NO2
0 1 2 3
O3
0 1 2 3
PM2.5
0 1 2 3
PN
0 1 2 3
EC
0 1 2 3
pyrene
0 1 2 3
B[a]P
0 1 2 3
Total PAHs
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1-OH-pyrene
-20
0
20
40
60
Perc
ent changes in 1
-OH
P
per
IQR
incre
ases in p
ollu
tants
Pollutant * Lag
0 1 2 3
CO
0 1 2 3
NO2
0 1 2 3
O3
0 1 2 3
PM2.5
0 1 2 3
PN
0 1 2 3
EC
0 1 2 3
pyrene
0 1 2 3
B[a]P
0 1 2 3
Total PAHs
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• The formation of DNA and protein adducts
from benzo[a]pyrene
Exposure Biomarker for diesel nitro-PAHs
Hemoglobin adducts
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Biomarkers of physiological response /
pathway
Particulate Matter
Epithelial cells•Mitochondria•NADPH oxidase
Fenton reactions•Transit metals: Fe, Cu, V, Cr, etc
Inflammation•Macrophage cells• iNOS (NO synthase)
DNA oxidation Lipid peroxidation • Oxidation of NO
8-OHdG MDA
ω-6-polyunsaturated acidsDNA repair
RS-NO RS-H
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Biomarkers of physiological response / pathway
malondialdehyde (MDA)
Spectrophotometry
(TBARS)
Rapid
Easy
Economical
Less specific
Less sensitive
Less reproducible
HPLC-FL
Specific
Reproducible
Easily available
Require derivatization
GC-MSMS
Specific
Reproducible
Sensitive
Pre-treatment required
On-fibrederivatization
LC-MSMS
Specific
Reproducible
Sensitive
Costly
Derivatizationrequired
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• Free MDA VS Total MDA
– Broncho-alveolar lavage fluid (BALF)
– Urine
– Serum
Biomarkers of physiological response / pathway
malondialdehyde (MDA)
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y = 0.2053x - 2.2772
R² = 0.7868
0
500
1000
1500
2000
2500
0.0 2000.0 4000.0 6000.0 8000.0 10000.0 12000.0
Fre
e M
DA
(n
M)
Total MDA (nM)
Free and total MDA
Urine
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Free and total MDA
Serum
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
Total MDA Free MDA
MD
A c
on
cen
tra
tin
(µ
M)
Asthmatic non-Asthmatic
**
*
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Biomarkers of physiological response / pathway
Animal Inhalation Chambers
Flow rate= 35 L/minVelocity= 0.0004 m/sTemp= 24 ± 1 ᵒCLighting= natural day/night cycle
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Biomarkers of physiological response / pathway
MDA: Animal Inhalation Chambers
Pregnant rats after
14 day exposure
Pups at 3 or 8 wks
old (male + female)
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-15
-10
-5
0
5
10
15
20
25
30
Lag0 Lag1 Lag2 Lag3 Lag4 Lag5 Lag6 Lag0 Lag1 Lag2 Lag3 Lag4 Lag5 Lag6
% changes in EBC MDA associated with IQR increases in
ambient SO2 and PM2.5
SO2 PM2.5
Biomarkers of physiological response / pathway
MDA: Beijing Olympic study
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-10
-5
0
5
10
15
20
25
30
35
Lag0 Lag1 Lag2 Lag3 Lag4 Lag5 Lag6 Lag0 Lag1 Lag2 Lag3 Lag4 Lag5 Lag6
% changes in Urine MDA associated with IQR increases in
ambient SO2 and PM2.5
Biomarkers of physiological response / pathway
MDA: Beijing Olympic study
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• Analyzing methods
Biomarkers of physiological response / pathway
8-hydroxy-2’-deoxyguanosine (8-OHdG)
LC-MSMS
• Specific
• More sensitive
HPLC-ECD
• Specific
• Sensitive
• Possible interferences from the biological matrix
ELISA
• Easy to perform
• Non-specific
• Lower reproducibility
Ref: Rapid Commun. Mass Spectrom. 2004; 18: 505-510
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Biomarkers of physiological response / pathway
Urinary 8-OHdG: Beijing Olympic study
-40
-20
0
20
40
60
80
100
120
Lag0 Lag1 Lag2 Lag3 Lag4 Lag5 Lag6 Lag0 Lag1 Lag2 Lag3 Lag4 Lag5 Lag6
% changes in urine 8-OHdG associated with IQR increases in
ambient SO2 and PM2.5
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• HPLC-UV
– Sensitive
– Reproducible
– Easy to perform (no pretreatment required for
exhaled breath condensate and BALF samples)
Biomarkers of physiological response / pathway
Nitrite
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-15
-10
-5
0
5
10
15
20
25
30
35
Lag0 Lag1 Lag2 Lag3 Lag4 Lag5 Lag6 Lag0 Lag1 Lag2 Lag3 Lag4 Lag5 Lag6
% changes in EBC Nitrite associated with IQR increases in
ambient SO2 and PM2.5
Biomarkers of physiological response / pathway
Nitrite: Beijing Olympic study
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Jake Chung
Mingquan Li
Xiaoxing Cui
Drew Day
Marlyn Duarte
PI: Junfeng (Jim) Zhang
Jicheng Gong
Hailong HanLinchen He