Registration

Breakfast Meetings:

Student and New Investigator Breakfast
Baker Room

Chairperson: Olga Kovalchuk, University of Lethbridge

Chairpersons: Ronald D. Snyder, Schering-Plough Research Institute and Martyn T. Smith, University of California, Berkeley

Co-Sponsored by Amgen, Inc.

TOPICAL REVIEW 3: DNA Repair Machines

Description

Speaker: John A. Tainer, The Scripps Research Institute and Lawrence Berkeley National Laboratory

TOPICAL REVIEW 4: Environmental Epigenomics in Human Health and Disease

Description

Speaker: Randy L. Jirtle, Duke University Medical Center

SYMPOSIUM 8: Nucleotide Pool Damage and its Biological Consequences

Aberrant oxidation is a property of many tumor cells. Oxidation of nucleotide pool, i.e., dNTPs, as well as DNA is a major source of spontaneous mutagenesis, carcinogenesis and other degenerative diseases. Here, we discuss the mechanisms involved in oxidized dNTPs resulting in genome instability and how cellular defense systems combat with these endogenous insults.

Chairpersons: Takehiko Nohmi, National Institute of Health Sciences and Margherita Bignami, Instituto Superiore di Sanità

The Roles of Y-Family DNA Polymerases in Oxidative Mutagenesis

Speaker: Takehiko Nohmi, National Institute of Health Sciences

Metabolism and Incorporation of Exogenous
8-oxodG into DNA in Cell Culture and Mice: An Alternative Promutagenic Pathway Compared to Oxidation of Nucleotides and DNA

Speaker: Paul T. Henderson, Lawrence Livermore National Laboratory

Defenses Against Damage in Nucleotide Pools and the Suppression of Carcinogenesis, Neurodegeneration, and Heart Failure

Reduced Huntington’s Disease-Like Striatal Neurodegeneration in Mice Expressing a Human 8-oxodGTPase

Speaker: Margherita Bignami, Instituto Superiore di Sanità

SYMPOSIUM 9: Germ Cells and Transgenerational Effects

The goal of this symposium is to highlight new findings and approaches in investigating heritable effects and to discuss novel and unusual mechanisms of germ cell effects on the wellbeing of the offspring. New evidence is emerging that implicates epigenetic modifications of the genome as a critical and poorly understood mechanism resulting in genetic disease. Speakers in this symposium will present research demonstrating that epigenetic modifications can arise in the germline as a result of subtle environmental exposures, and that these changes may persist and influence genetic disease outcome for many generations. Topics covered include (1) instability arising at low doses of exposure; (2) use of new model systems to measure transgenerational effects; and (3) stable and heritable epigenetic changes that result in alterations in gene transcription and health effects in offspring.

Chairpersons: Francesco Marchetti, Lawrence Berkeley National Laboratory and Yuri E. Dubrova, University of Leicester

Transgenerational Effects in Mammals: A Story of a Stable Instability

Speaker: Yuri E. Dubrova, University of Leicester

Germ-Cell Mediated Genomic Instability: Fishing for Answers

Speaker: Richard N. Winn, University of Georgia

Setting and Perturbing DNA Methylation Patterns in Male Germ Cells: Consequences for Fertility and the Next Generation

Speaker: Jacquetta Trasler, McGill University

Mainstream Tobacco Smoke Causes Paternal Germline DNA Sequence Mutation

Speaker: Carole Yauk, Health Canada (Presented by George Douglas, Health Canada)

Effects of Second-Hand Smoke on Male Germ Cells and Early Embryonic Development

Speaker: Francesco Marchetti, Lawrence Berkeley National Laboratory

SYMPOSIUM 10: Challenges in Assessing Risk from Low-Dose Chemical Exposures

Most experimental data from animal studies are conducted at high doses, shorter time period and to single chemicals. However, human are exposed to lower doses, for longer time and to multiple chemicals. Therefore, estimation of human risk due to long-term exposure to very low doses in the environment poses a number of biological and statistical challenges. Biological challenges include lack of positive response at very low doses due to shorter duration of exposure, availability of data in animal studies and not in human studies etc. One of the statistical problems is to extrapolate the animal dose-response relation from the high dose levels where data are available to low dose, which humans might encounter. The purpose of this symposium is to illustrate a number of these issues through a discussion of the available information at low doses using specific examples of chemicals.

Chairpersons: Nagu Keshava, U.S. Environmental Protection Agency and Paul A. White, Health Canada

Sponsored by U.S. Environmental Protection Agency­Grant # EP07H000535

Challenges in Assessing Risk from Low-Dose Chemical Exposures

Use of Toxigenomics to Identify Carcinogenic MOA to Inform Dose-Response Decisions

Speaker: Jiri Aubrecht, Pfizer Inc.

Availability of Data in the Low Dose Region and Their Uses in Risk Assessment

Speaker: Jeffrey Ross, U.S. Environmental Protection Agency

Testing for Additivity in the Low Dose Region of an Environmentally Relevant Mixture of 18 PHAHs with Discussion for Guidelines on Use

Speaker: LeAnna G. Stork, Monsanto

Application of Mode of Action and Dose-Response Information in a Chemical Mixtures Risk Assessment

Speaker: Jason Lambert, U.S. Environmental Protection Agency

EMS Technology Lunchtime Workshop: Current Applications of the Comet Assay
(Free Workshop, Advance Registration Required, Lunch Provided, Seating Limited)

The Comet assay is a relatively simple and sensitive microgel electrophoresis technique for the detection of DNA damage and its repair in individual eukaryotic cells. The assay is used extensively in Genotoxicity testing, using both in vitro and in vivo test systems; in human and environmental biomonitoring studies to detect exposure to genotoxic agents; and in mechanistic studies to evaluate DNA repair pathways. This workshop will focus on recent developments in the validation of the in vivo Comet assay for detecting genotoxic substances, developments in DNA repair studies and human biomonitoring.

Chairpersons: Patricia Escobar, BioReliance and Raymond Tice, National Institute of Environmental Health Sciences

Sponsored by BioReliance

General Overview of the Comet Assay

Speaker: Diana Anderson, University of Bradford

Update in the International Validation of the In Vivo Comet Assay

Speaker: Yoshifumi Uno, Mitsubishi Pharma Corporation, Japan

Estimating DNA Repair in Human Cells With the Comet Assay

Speaker: Andrew Collins, University of Oslo

The Comet Assay Used for Biomonitoring in Human Population Studies

Speaker: Maria Dusinska, Norwegian Institute for Air Research (NILU)

Discussion

EMS Policy Lunchtime: Is it Time to Amend the Core Genetic Toxicity Testing Battery? The Mutagenicity Test Battery Reconsidered
(Free Workshop, Advance Registration Required, Lunch Provided, Seating Limited)

This Workshop discusses various topics related to the current battery of short-term tests for genotoxicity. Consideration is given to current data regarding the usefulness of this battery of tests for detecting mutagens and potential rodent and/or human carcinogens. Also, the limitations of this battery will be discussed, with special emphasis on new developments in the field and what new endpoints might be useful to add to the current test battery—if any.

Chairpersons: David M. DeMarini, U.S. Environmental Protection Agency, and David A. Eastmond, University of California–Riverside

Sponsored by Covance Laboratories Ltd. UK, and the National Toxicology Program, National Institute of Environmental Health Sciences

Introduction

Speaker: David M. DeMarini, U.S. Environmental Protection Agency

A Historical Perspective on the Current Test Battery: Its Strengths and Weaknesses

Speaker: Errol Zeiger, Errol Zeiger Consulting

European Legislation and the Need for More Predictive In Vitro Tests

Speaker: David J. Kirkland, Covance Laboratories Ltd. UK

New Strategies for Improving the Predictivity of Short-Term Tests

Speaker: Ronald D. Snyder, Schering-Plough Research Institute

Discussion

SYMPOSIUM 11: The Replication of Damaged DNA

Environmental and endogenous agents produce lesions in DNA frequently enough that adducts are sometimes encountered by the DNA replication machinery before they can be removed by DNA repair. Such encounters are potentially mutagenic. New research is revealing the functions of replicative and specialized DNA polymerases in handling damage in the genome. The speakers in this symposium will cover the latest genetic, structural, and biochemical information on the different pathways available to cells to achieve replication of DNA that contains lesions.

Chairpersons: Graham C. Walker, Massachusetts Institute of Technology and Richard D. Wood, University of Pittsburgh

Studies of Leading and Lagging Strand DNA Replication Fidelity in Yeast

Speaker: Thomas A. Kunkel, National Institute of Environmental Health Sciences

Visualizing a Replicative DNA Polymerase Encounter Unrepaired Free Radical DNA Lesions

Speaker: Sylvie Doublié, University of Vermont

A Hand-Off Mechanism for Primosome Assembly in Replication Restart

Speaker: James L. Keck, University of Wisconsin–Madison

Suppression of Genomic Instability by the Mammalian RAD5 Pathway Through PCNA Polyubiquitination

Speaker: Kyungjae Myung, National Human Genome Research Institute

Function and Control of Translesion DNA Polymerases

Speaker: Graham C. Walker, Massachusetts Institute of Technology

SYMPOSIUM 12: Assessment of the Technologies for Molecular Biodosimetry for Human Low-Dose Radiation Exposure

Biodosimetry, the estimation of received doses by determining biological responses within cells, tissues and whole organisms is rapidly expanding due to modern genomic approaches. This series of talks discusses current model systems and biological mechanisms, highlighting modern approaches to individual radiation biodosimetry.

Chairperson: Matthew A. Coleman, Lawrence Livermore National Laboratory and Narayani Ramakrishnan, National Institute of Allergy and Infectious Diseases

Sponsored by the Office of Sciences (BER), U.S. Department of Energy Grant No. DE-FG02-07ER64474 and the National Institute of Allergy and Infectious Diseases

Model Systems and Current Approaches in Biodosimetry

Speaker: Matthew A. Coleman, Lawrence Livermore National Laboratory

Brief Overview of Biodosimetry Projects in the NIH Rad/Nuc Program

Speaker: Narayani Ramakrishnan, National Institute of Allergy and Infectious Diseases

Rapid Assessment of Gene Expression Signatures for Biodosimetry

Speaker: Sally Amundson, Columbia University

Persistence of Gene Expression Changes Following Low Doses of Ionizing Radiation

Speaker: James D. Tucker, Wayne State University

Flow Cytometric Scoring of Radiation-Induced Micronuclei: Reticulocyte- and Lymphocyte-Based Approaches

Speaker: Stephen D. Dertinger, Litron Laboratories

In Vivo Murine Dose-Response Calibration Curves for Early-Response Exposure Assessment Using Multiple Radiation-Responsive Blood Protein Biomarkers

Speaker: Natalia I. Ossetrova, Armed Forces Radiobiology Research Institute

Determination of Marker Genes for the Exposure of Aristolochic Acid in Rat Kidney by Cross-Platform Comparison and Biological Function Choice

Speaker: Tao Chen, National Center for Toxicological Research, U.S. Food and Drug Administration

SYMPOSIUM 13: Use of Genotoxicity Data in Mode of Action Analysis for Human Health Risk Assessment

Many chemicals and stressors interact with DNA via various genotoxicity mechanisms that can lead to adverse human health outcomes such as cancer, developmental/reproductive defects, and heritable effects. Understanding the genotoxic mode of action (MOA) of these agents can be key to identifying processes that may cause chemical exposures to differentially affect a particular endpoint, a particular target, or a particular segment of the population/life-stage. It is important to assess a possible genotoxic MOA since, for example, the U.S. Environmental Protection Agency released Guidelines for Carcinogen Risk Assessment and Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens that require consideration of all available data, including genotoxicity data, to understand the MOA for carcinogenicity of a particular chemical. It is equally important to consider how the genotoxicity of a compound impacts diseases other than cancer. Presentations in this Symposium discuss how genotoxicity data may be used in a MOA analysis for various human health risks.

Chairpersons: Channa Keshava, U.S. Environmental Protection Agency, and Kerry L. Dearfield, USDA, FSIS, OPHS

Sponsored by U.S. Environmental Protection Agency–Grant # EP07H000535

Use of Genotoxicity Data in Mode of Action Analysis for Human Health Risk Assessment

Speaker: Channa Keshava, U.S. Environmental Protection Agency

Establishing a Carcinogenic Mode of Action Using Mutagenicity Data

Speaker: Rita Schoeny, U.S. Environmental Protection Agency

Use of Genotoxicity Data to Assess Linearity of Carcinogenic Response

Speaker: David A. Eastmond, University of California–Riverside

Cytogenetic Damage and Genetic Variants in Individuals Susceptible to Arsenic-Induced Cancer

Speaker: Ashok K. Giri, Indian Institute of Chemical Biology

Mode of Action Analysis to Address Heritable Mutations: Acrylamide as an Example

Speaker: Kerry L. Dearfield, USDA, FSIS, OPHS

PLENARY LECTURE: Is There a Human Risk from Potent Mutagens in Cooked Meat?

The most potent mutagens known are eaten daily by most Americans. This lecture discusses their risk for humans and examines their carcinogenic mechanisms. Emphasis is on formation, absorption, metabolism, DNA damage, mutagenesis, repair and cell proliferation related to these heterocyclic amines. Both rodent and human studies are compared and discussed for their relevance to risk. The utilization of special technologies like accelerator mass spectrometry is emphasized for use in comparing genetic damage in humans to polymorphism conferring susceptibility.

Speaker: James S. Felton, Lawrence Livermore National Laboratory

Poster Session II and Exhibits (Poster Assignments)

Committee Meetings: