chemical sensitivity NIH NIEHS human susceptibility to environmental agents

[Guest guest]

" NIEHS Environmental Genome Project (EGP) is working to systematically identify

and characterize common sequence polymorphisms in many genes with suspected

roles in determining chemical sensitivity. The rationale of the EGP is that

certain genes have a greater than average influence over human susceptibility to

environmental agents. If we identify and characterize the polymorphism in those

genes, we will increase our

understanding of human disease susceptibility. This knowledge can be used to

protect susceptible individuals from disease and to reduce adverse exposure and

environmentally induced disease. "

1: Mutat Res. 2003 Nov;544(2-3):349-60.

The impact of new technologies on human population studies. Waters MD,

Selkirk JK, Olden K. National Center for Toxicogenomics, 111 Drive,

P.O. Box 12233, MD F1-05, Research Triangle Park, NC 27709-2233, USA.

waters2@... Human population studies involve clinical or

epidemiological observations that associate environmental exposures with health

endpoints and disease. Clearly, these are the most sought after data to support

assessments of human health risk from environmental exposures. However, the

foundations of many health risk assessments rest on experimental studies in

rodents performed at high doses that elicit adverse outcomes, such as organ

toxicity or tumors. Using the results of human studies and animal data, risk

assessors define the levels of environmental exposures that may lead to disease

in a portion of the population. These decisions on potential health risks are

frequently based on the use of default assumptions that

reflect limitations in our scientific knowledge. An important immediate goal

of toxicogenomics, including proteomics and metabonomics, is to offer the

possibility of making decisions affecting public health and public based on

detailed toxicity, mechanistic, and exposure data in which many of the

uncertainties have been eliminated. Ultimately, these global technologies will

dramatically impact the practice of public health and risk assessment as applied

to environmental health protection. The impact is already being felt in the

practice of toxicology where animal experimentation using highly controlled

dose-time parameters is possible. It is also being seen in human population

studies where understanding human genetic variation and genomic reactions to

specific environmental exposures is enhancing our ability to uncover the causes

of variations in human response to environmental exposures. These new

disciplines hold the promise of reducing the costs and time

lines associated with animal and human studies designed to assess both the

toxicity of environmental pollutants and efficacy of therapeutic drugs.

However, as with any new science, experience must be gained before the promise

can be fulfilled. Given the numbers and diversity of drugs, chemicals and

environmental agents; the various species in which they are studied and the

time and dose factors that are critical to the induction of beneficial and

adverse effects, it is only through the development of a profound knowledge

base that toxicology and environmental health can rapidly advance. The National

Institute of Environmental Health Sciences (NIEHS), National Center for

Toxicogenomics and its university-based Toxicogenomics Research Consortium

(TRC), and resource contracts, are engaged in the development, application and

standardization of the science upon which to the build such a knowledge base on

Chemical Effects in Biological Systems (CEBS). In addition,

the NIEHS Environmental Genome Project (EGP) is working to systematically

identify and characterize common sequence polymorphisms in many genes with

suspected roles in determining chemical sensitivity. The rationale of the EGP

is that certain genes have a greater than average influence over human

susceptibility to environmental agents. If we identify and characterize the

polymorphism in those genes, we will increase our understanding of human

disease susceptibility. This knowledge can be used to protect susceptible

individuals from disease and to reduce adverse exposure and environmentally

induced disease. PMID: 14644337 [PubMed - indexed for MEDLINE] Related

Links Toxicology and genetic toxicology in the new era of

" toxicogenomics " : impact of " -omics " technologies. [Mutat Res. 2002]

PMID:11804602 Toxicogenomic approach for assessing toxicant-related

disease. [Mutat Res. 2003] PMID:14644344 Health-related disparities:

influence

of environmental factors. [Med Clin North Am. 2005] PMID:15925646

Risk management frameworks for human health and environmental risks. [J Toxicol

Environ Health B Crit Rev. 2003] PMID:14698953 Systems toxicology and

the Chemical Effects in Biological Systems (CEBS) knowledge base. [EHP

Toxicogenomics. 2003] PMID:12735106 -end-

Definitions (from http://www.medterms.com):

Toxicogenomics: The collection, interpretation, and storage of information

about gene and protein activity in order to identify toxic substances in the

environment, and to help treat people at the greatest risk of diseases caused by

environmental pollutants or toxicants.

Metabonomics: The study of metabolic responses to drugs, environmental changes

and diseases. Metabonomics is an extension of genomics (concerned with DNA) and

proteomics (concerned with proteins). Following on the heels of genomics and

proteomics, metabonomics may lead to more efficient drug discovery and

individualized patient treatment with drugs, among other things.

In more technical (and wordy) terms, metabonomics is the quantitative

measurement of the dynamic multiparametric metabolic response of living systems

to pathophysiological stimuli or genetic modification. See also: Metabolomics.

Metabolomics: The global analysis of metabolites, small molecules generated in

the process of metabolism.

Proteomics: The study of the proteome, the complete set of proteins produced

by a species, using the technologies of large-scale protein separation and

identification. The term proteomics was coined in 1994 by Marc Wilkins who

defined it as " the study of proteins, how they're modified, when and where

they're expressed, how they're involved in metabolic pathways and how they

interact with one another. "

Polymorphism: A variation in the DNA that is too common to be due merely to

new mutation. A polymorphism must have a frequency of at least 1% in the

population.

Examples of polymorphisms include the genes for sickle cell disease,

thalassemia and G6PD deficiency. These genes are widely believed to offer an

advantage against malaria.

__________________________________________________