There are three broad categories of molecular biomarkers that are commonly used in the field of environmental health:

Biomarkers of exposure – quantify body burden of chemicals or metabolites and are usually applied early in the exposure-disease paradigm. These markers are powerful tools for epidemiologists, allowing relatively accurate measurement of external and/or internal dose of an environmental agent. However, the applicability of biomarkers of exposure is often limited by their relatively short-half life, providing information on exposure over a period of days to months compared to the natural history of the disease that spans years or decades. There are noteworthy exceptions to the transient nature of exposure biomarkers, such as pesticide residues in body fat and blood that can persist over months and years. Nevertheless, the timing of sample acquisition for measurement of environmental exposures and the study of interactions with genetic susceptibilities is a critical factor in study design.
Biomarkers of effect – detect functional change in the biological system under study, and allow investigators to predict the outcome of exposure. DNA damage (e.g. adducts, chromosomal aberrations, loss of heterozygosity at specific chromosome loci) is frequently used as biomarkers of effect, although there is often no clear delineation from biomarkers of exposure. For example, DNA adducts can be interpreted as biomarkers both of exposure and biological effect.
Biomarkers of susceptibility – indicates the inter-individual variation in mechanistic processes on the continuum between exposure and effect. An individual’s susceptibility to environmentally-mediated disease may arise from genetic causes or from non-genetic factors such as age, gender, disease state, or dietary intake. Genetic polymorphisms may function as biomarkers of susceptibility; but it is important to keep in mind that it is actually the phenotype that is of importance for the final response to the hazardous insult.
The SBRP has made a large investment in biomarker research over the years and, in fact, this Program has supported some of the leaders in the field. Early research supported by the Program focused on the identification of potential biomarkers. These studies involved animal models and human samples. Promising biomarkers have been further validated in limited human studies. As the Program has matured, we are beginning to realize the payoff for these earlier investments. We are seeing a shift in the SBRP portfolio from biomarker development to the application of these biomarkers in molecular epidemiology studies, and in some cases, biomarkers that have been developed with SBRP support are moving to clinical application. Biomarker development, validation and application clearly require a long-term commitment to realize the benefits of our investment. We intend to continue strong support in this area of research.

Toxicogenomics:
Environmental Health Perspectives, Toxicogenomics
Toxicogenomics: An Emerging Discipline, Environmental Health Perspectives (Vol. 110, Num. 12, Dec. 2002)
National Center for Toxicogenomics (NCT)
National Toxicology Program
National Center for Human Genome Research
Woodrow Wilson Center for International Scholars

Application of Biomarkers to Environmental Health and Risk Assessment
FY 2004 Science to Achieve Results (STAR) Program
National Center for Environmental Research
http://es.epa.gov/ncer/rfa/2004/2004_biomarkers.html

Bay, S.M., D. Lapota, J. Anderson, J. Armstrong, T. Mikel, A.W. Jirik, and S. Asato. 2000. Southern California Bight 1998 Regional Monitoring. Program: IV. Sediment Toxicity. Southern California Coastal Water Research Project. Westminster, CA.
Sediment extracts from 268 stations were evaluated for toxicity using the P450 human reporter gene system (HRGS) test, which measures the concentration of organic compounds that induce the cytochrome P450 enzyme system (e.g., PAHs, dioxins, furans, and some PCBs).
ftp://www.sccwrp.org/pub/download/PDFs/bight98sedtoxrpt.pdf

Southern California Bight 1998, Regional Monitoring Program:
Executive Summary
ftp://ftp.sccwrp.org/pub/download/PDFs/bight98executive_summary.pdf
documents: http://www.sccwrp.org/regional/98bight/98docs.htm

Author Anderson, J.W., J.M. Jones, J. Hameedi, E. Long, R.H. Tukey
Title: Comparative analysis of sediment extract from NOAA's bioeffects studies by the biomarker P450 reporter gene system. Journal Title Marine Environmental Research
Publication Information 1999.
Abstract
Sediment samples collected from nine coastal and estuarine areas have been analyzed to determine response of a biomarker, P450 Reporter Gene System (RGS). This biomarker, using a transgenic cell line, detects the presence and potency of organic compounds that typically induce the CYPIA gene. Previous investigations have shown that sediments containing chemicals which produce a response of 60 or more ug/g of benzo[a]pyrene equivalents (B[a]PEq) also exhibited a degraded community structure. RGS data from all study areas combined (527 samples) show that the mean response is 22.7 ug/g B[a]Peq, and the mean upper 99% confidence interval is 32. We believe that sediments exhibiting B[a]PEq values of 32-60 are possibly contaminated to the extent that effects on benthic organisms may be observed, and those producing an RGS response of 60 and greater are likely to contain levels of chemicals that will produce chronic toxicity. The majority of the stations investigated produced responses below 32ug/g B[a]Peq. No samples from coastal southern California produced responses greater than 39. However, samples producing induction over 60 ug/g B[a]Peq were:50%, San Diego Bay;16%, Delaware Bay; 8%, Sabine Lake; 4%, Northern Puget Sound; and 3%, Charleston Harbor. A strong statistical correlation was observed between the RGS responses and high molecular weight polycyclic aromatic hydrocarbon concentrations in the sediments from several of the study area. Of the 2694 km2 encompassed in the surveys, only 0.42% of the area exhibited responses above 32 ug/g B[a]Peq, which represented 11.4 km2. This assay is useful in identifying high levels of toxic and carcinogenic compounds in the sediments and predicting the potential impact of these chemicals on the biological community. This work was supported by NOAA's National Centers for Coastal Ocean Science, Center for Coastal Monitoring and Assessment.
Keywords comparative analysis, bioeffect studies, biomarker P450, reporter gene system, RGS, Center for Coastal Monitoring and Assessment, CCMA
http://www6.nos.noaa.gov/noslib/pubdisplay.lasso?-KeyValue=33136&-Token.Action=

Comparisons between CYP1A1-inducing chemicals in sediments of San Francisco Bay and chemical and biological measurements. Anderson, J.W., I. Hartwell and J. Hameedi
Abstract http://www.aehms.org/SQA5_anderson.html
The San Francisco Bay was the subject of studies by NOAA and EPA in 2000 and by NOAA in 2001. In each year, 99 sediment samples distributed within strata over the entire Bay were collected and analyzed for a range of chemical and biological parameters. A biomarker assay, P450 Human Reporter Gene System (EPA Method 4425), was used to document the occurrence and distribution of CYP1A1-inducing compounds in these samples. The assay utilizes a stably transfected human hepatoma cell line with a plasmid containing the firefly luciferase gene downstream of CYP1A1 promoter sequences. When these cells are exposed to CYP1A1-inducing compounds (PAHs, PCBs, and dioxins/furans), luciferase is produced, and can be easily measured with a luminometer. The responses, expressed as mg of benzo[a]pyrene equivalents/g (B[a]PEq) from samples collected in 2000 and 2001 were quite similar (means = 21.2, 19.9; upper 99% confidence limits = 28.0, 26.9). Each year 5 stations were over 60 mg/g B[a]PEq, and the numbers of samples above the upper confidence limit were 20 and 17. The PAHs were most highly correlated with the 4425 responses (R2 values = 0.64, 0.63). At several of the stations, but not all, a high 4425 response was observed when there was a significant reduction in normal development of sea urchin embryos. In 2000, splits of extracts were first cleaned of PAHs by silica gel before 4425 testing and the results compared to high-resolution GC/MS analyses of dioxins, furans, and PCBs of 63 samples. Most samples were less than the HRGS reporting limit of 10 ng/Kg TEQ, which was confirmed GC/MS and only one sample was significantly higher by GC/MS. Method 4425 is an inexpensive and rapid screening tool for determining which of the numerous sediment locations sampled contain significant levels of carcinogenic and toxic compounds, and are therefore likely to exhibit degraded biological communities.

Biomarkers of Environmentally Associated Disease: Technologies, Concepts, and Perspectives
by Samuel H. Wilson (Editor), William A. Suk (Editor), Bergman (Contributor), Max Costa (Contributor), Denison (Contributor) (2002)
Book Info
Covers the current status and future prospects of biomarker research and addresses DNA metabolism, pathophysiology, nanotechnology, and more. Focuses on the risk of exposure to persistent organic pollutants, heavy metals, airborne toxics, environmental estrogens, and other environmental pollutants.
Book Description
The end of the 20th century brought with it a revolution in molecular biology that culminated in advances such as the completion of the human genome. This has brought optimism to the fields of toxicology and environmental health, and the anticipation that molecular biomarkers might soon come of age and have a major impact on human and environmental health. Biomarker research is an area of current interest to scientists in a number of fields that are concerned with environmental exposure to pollutants and environmentally associated disease.Biomarkers of Environmentally Associated Disease: Technologies, Concepts, and Perspectives provides comprehensive coverage of the current status and future prospects of a field that will play a key role in emerging areas of public health and medicine. It focuses on the risk to human and environmental health of exposure to persistent organic pollutants, heavy metals, airborne toxics, environmental estrogens, and other environmental pollutants. This material will aid researchers in understanding, treating, and preventing environmentally induced disease.Validated molecular biomarkers have long been recognized as invaluable tools for identifying and preventing human disease. As biomarkers begin to be applied more widely, it is also important to assure that they are implemented ethically, with attention to the social and legal issues associated with their use. Biomarkers of Environmentally Associated Disease is an outstanding resource providing state-of-the-art information for the fields that encompass molecular biomarkers.

8. Use of Biomarkers for Environmental Quality Assessment by Laurent Lagadic (Editor), et al (Hardcover - January 2001) Editorial Reviews
From Book News, Inc.
Presents examples of the use of biomarkers in the monitoring of terrestrial, freshwater, and marine environment quality. Examples are critically analyzed by environmental scientists involved in fields of biomarkers. On the basis of this analysis, proposals are made for improvement of assessment of environmental effects of pollutants using biomarkers. Possibilities of linking biomarker responses with effects of pollutants at higher levels of biological organization are also addressed. Lagadic in a researcher at the Joint Research Unit for Fish Physiology, Biodiversity and the Environment at the Institut National de la Recherche Agronomique, France.Book News, Inc.®, Portland, OR

9. Bioindicators and Biomarkers of Environmental Pollution and Risk Assessment
by Jamil Kaiser, et al (Hardcover - April 2001)
Editorial Reviews
From Book News, Inc.
Jamil is with the Indian Institute of Chemical Technology in Hyderabad. Here he describes the biological monitoring of pollution in order to conserve the biological diverse species and the integrity of natural ecosystems, even if that means taking preventative measures. He surveys species that have been and are being used in specific environments and to signal specific hazards, starting with the traditional canary in the coal mine.Book News, Inc.®, Portland, OR

For Superfund, the National Priorities List (NPL) presently lists 1,232 sites and an estimated 40 new sites will be added annually through at least 2010. Also, there are more than 300,000 Leaking Underground Storage Tank (LUST) Sites requiring Corrective Action; states spend nearly $2 billion annually to clean up these sites. Additionally, it is estimated there are potentially hundreds of thousands of old gas stations that may require remediation. Annually, 18,000 to 24,000 oil spills are reported and 10 million to 25 million gallons of oil are spilled, impacting coastal and inland waterways. http://www.epa.gov/OSP/myp/csites.pdf

RE Funding:
EPA cleaned up only 42 toxic waste sites in 2002, down more than 50% from the late 1990's. Instead of polluters paying to clean up their toxic waste, taxpayers will likely pay 79 percent or more of program costs in 2004, up from 18 percent in 1996, and will pay for nearly the entire program in 2005. Superfund's original 'polluter pays' funding mechanism expired in 1995, and Superfund's trust fund, at a high of $3.6 billion in 1995, will be nearly exhausted by the end of 2004, leaving taxpayers to pay for the entire program. Former Presidents Reagan, George H.W. Bush, and Clinton all collected and supported reinstatement of the polluter pays fees, but the Bush Administration has expressed its opposition to reinstating the fees.
(excerpt from http://www.commondreams.org/news2003/0717-09.htm)

PUBLICATIONS:

Author Anderson, J.W., J.M. Jones, J. Hameedi, E. Long, R.H. Tukey
Title Comparative analysis of sediment extract from NOAA's bioeffects studies by the biomarker P450 reporter gene system. Journal Title Marine Environmental Research. Publication Information 1999. http://www6.nos.noaa.gov/noslib/pubdisplay.lasso?-KeyValue=33136&-Token.Action=

Abstract
Sediment samples collected from nine coastal and estuarine areas have been analyzed to determine response of a biomarker, P450 Reporter Gene System (RGS). This biomarker, using a transgenic cell line, detects the presence and potency of organic compounds that typically induce the CYPIA gene. Previous investigations have shown that sediments containing chemicals which produce a response of 60 or more ug/g of benzo[a]pyrene equivalents (B[a]PEq) also exhibited a degraded community structure. RGS data from all study areas combined (527 samples) show that the mean response is 22.7 ug/g B[a]Peq, and the mean upper 99% confidence interval is 32. We believe that sediments exhibiting B[a]PEq values of 32-60 are possibly contaminated to the extent that effects on benthic organisms may be observed, and those producing an RGS response of 60 and greater are likely to contain levels of chemicals that will produce chronic toxicity. The majority of the stations investigated produced responses below 32ug/g B[a]Peq. No samples from coastal southern California produced responses greater than 39. However, samples producing induction over 60 ug/g B[a]Peq were:50%, San Diego Bay;16%, Delaware Bay; 8%, Sabine Lake; 4%, Northern Puget Sound; and 3%, Charleston Harbor. A strong statistical correlation was observed between the RGS responses and high molecular weight polycyclic aromatic hydrocarbon concentrations in the sediments from several of the study area. Of the 2694 km2 encompassed in the surveys, only 0.42% of the area exhibited responses above 32 ug/g B[a]Peq, which represented 11.4 km2. This assay is useful in identifying high levels of toxic and carcinogenic compounds in the sediments and predicting the potential impact of these chemicals on the biological community. This work was supported by NOAA's National Centers for Coastal Ocean Science, Center for Coastal Monitoring and Assessment.
Keywords: comparative analysis, bioeffect studies, biomarker P450, reporter gene system, RGS, Center for Coastal Monitoring and Assessment, CCMA

Editor: Wilson, Samuel H., 1939-
Title: Biomarkers of environmentally associated disease : technologies, concepts, and perspectives / [edited by] Samuel H. Wilson, William A. Suk
Publisher: Boca Raton : Lewis Publishers, c2002

Bay, S.M., D. Lapota, J. Anderson, J. Armstrong, T. Mikel, A.W. Jirik, and S. Asato. 2000. Southern California Bight 1998 Regional Monitoring Program: IV. Sediment Toxicity. Southern California Coastal Water Research Project. Westminster, CA.

Sediment extracts from 268 stations were evaluated for toxicity using the P450 human reporter gene system (HRGS) test, which measures the concentration of organic compounds that induce the cytochrome P450 enzyme system (e.g., PAHs, dioxins, furans, and some PCBs).
ftp://www.sccwrp.org/pub/download/PDFs/bight98sedtoxrpt.pdf

NIEHS SBRP | Volume I
Journals Most Frequently Published in by SBRP Scientists (1995-2002*)
TOTAL SBRP PUBLICATIONS by JOURNAL
Environmental Health Perspectives ­ 156
Environmental Science & Technology ­ 136
The Toxicologist ­ 101
Toxicological Sciences ­ 93
Toxicology and Applied Pharmacology ­ 85
Environmental Toxicology and Chemistry ­ 79
Applied and Environmental Microbiology ­ 58
Carcinogenesis ­ 52