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