university of cincinnati center for environmental genetics biomonitoring and imaging facilities and...
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University of CincinnatiCenter for Environmental Genetics
Biomonitoring and Imaging Facilities and Services Core
Core Members
Glenn Talaska, Ph.D., CIH, Core Leader
Marian Miller, Ph.D., Imaging Head
Stacey Andringa, RA2, Imaging and Analysis
Consultative Resources:
Robert Bornschein, Ph.D.
Scott Clark, Ph.D., CIH
Carol Rice, Ph.D., CIH
Howard Shertzer, Ph.D.
David Warshawsky, Ph.D.
CEG
Biomonitoring and Imaging Facilities and Services Core
Services
Consultation, Analysis and Training Related to:
•DNA Adduct Analysis (Talaska, Warshawsky)
•Carcinogen Metabolites (Warshawsky, Talaska)
•Radical/Electrophile Scavenger and Enzyme Assays (Shertzer)
•Mass Spectroscopy Referral (Warshawsky)
•Imaging and Histological Phenotyping (Miller)
CEG
Biomonitoring and Imaging Facilities and Services Core
Services (Cont.)
Consultation Regarding:
•Review and Critique Exposure Assessment Strategies (Rice, Bornschein, Clark, Talaska)
•Selection of Exposure Metrics (Rice, Clark, Talaska)
•Exposure Reconstruction (Rice)
•Review Exposure Data (Rice, Talaska)
•Biological Monitoring (Talaska)
CEG
Biomonitoring and Imaging Facilities and Services Core
Biomarkers in human and animal studies can:
1. Reduce Misclassification
2. Document the extent of effect modification
1. Exposure : Exposure Interactions
2. Gene : Exposure Interactions
3. Determine Mechanisms
4. Serve as outcome variables
Interactions:
Effects of Age, Sex, etc
Effects of Chronic Exposure (Cumulative Effects)
Effects of Concomitant Exposure
Additive
Antagonistic
Potentiative
Synergistic
Non-smokers Blonde Tobacco Black Tobacco
Tobacco Type
0
40
80
120
160
200
4-A
BP-
Hb
(p
g/g
Hb
)
Acetylation Effects by Tobacco Type Smoked
Slow Fast
Arsenic and PAH Interactions
Finding the Mechanism(s) of Actions
Craig Evans
Andy Maier
Alvaro Puga
Brenda Schumann
Glenn Talaska
Arsenic and PAH Disease Interactions
• Lung Cancer
– Smoking and Occupational As exposure
– As comutagenesis with DNA-reactive agents?
• Skin Cancer– Synergy Unknown
BAPP450
BAP-7,8-oxide
BAP-7,8-diol
Epoxide Hydrolase
P450
BAP-7,8-diol-9,10-oxide
Glutathione-S-Transferase DNA
BAP-DNA Adducts
Mutation Initiation
Carcinogenesis
BAP-7,8,9-triol-10-mercapturate
Urinary Elimination
M As
0 5 10
Fo
ld c
ha
ng
e in
ad
du
ct
lev
el
1
10
100
0.1 M BaP
0.5 M BaP
1.0 M BaP
Ad
du
cts
/ m
M G
SH
5
10
15
MediumBSOGSH-ester
0 M As 5 M As 10 M As
hp
rt m
uta
nts
pe
r 1
06 ce
lls
5
10
15
20
0.5 M BaP2.5 M As
- -- -
++
++
Skin Arsenic +BAP Skin BAP
Treatment Groups
0
100
200
300
400
500
RA
L X
109
Effect of Arsenic on BAP DNA Adducts In VivoSkin
*Difference Not Significant
Lung arsenic+ BAP Lung BAP
Treatment Groups
0
5
10
15
20
25
RA
L X
109
Effect of Arsenic on BAP DNA Adducts In VivoLung
*P=0.044
Skin Arsenic Concentration (g/g)
0.08 0.10 0.12 0.14 0.16 0.18 0.20
RA
L x
109
0
200
400
600
800
1000
R= 0.54
M= 5220
B=-800
P=0.11
Carcinogen-DNA Adducts are Increased in Exfoliated Urothelial Cells
of Wives of Smokers: Biological Monitoring of Passive Smoke
Exposure
Scott Henn, Brenda Schumann and Glenn Talaska
Department of Environmental Health
Biomarkers in human and animal studies can:
1. Reduce Misclassification
2. Document the extent of effect modification
1. Exposure : Exposure Interactions
2. Gene : Exposure Interactions
3. Determine Mechanisms
4. Serve as outcome variables