The currently used methods for assessment of exposure
to chemical toxicants are based on measurement
of tissue toxin levels or on surrogate markers
of toxicity, termed biomarkers (e.g., peripheral blood
levels of hepatic enzymes or DNA adducts). Because
gene expression is a sensitive endpoint, gene expression
as measured with microarray technology may
be useful as a new biomarker to more precisely identify
hazards and to assess exposure. Similarly,
microarrays could be used in an environmentalmonitoring
capacity to measure the effect of potential
contaminants on the gene-expression profiles
of resident organisms. In an analogous fashion,
microarrays could be used to measure gene-expression
endpoints in subjects in clinical trials. The combination
of these gene-expression data and more
established toxic endpoints in these trials could be
used to define highly precise surrogates of safety.
ทมใ่าวส่า
Gene-expression profiles in samples from exposed
individuals could be compared to the profiles of the
same individuals before exposure. From this information,
the nature of the toxic exposure can be determined
or a relative clinical safety factor estimated.
In the future it may also be possible to estimate not
only the nature but the dose of the toxicant for a
given exposure, based on relative gene-expression
levels. This general approach may be particularly
appropriate for occupational-health applications, in
which unexposed and exposed samples from the
same individuals may be obtainable. For example,
a pilot study of gene expression in peripheral-blood
lymphocytes of Polish coke-oven workers exposed
to PAHs (and many other compounds) is under consideration
at the NIEHS. An important consideration
for these types of studies is that gene expression can
be affected by numerous factors, including diet,
health, and personal habits. To reduce the effects
of these confounding factors, it may be necessary
to compare pools of control samples with pools of
treated samples. In the future it may be possible to
compare exposed sample sets to a national database
of human-expression data, thus eliminating the
need to provide an unexposed sample from the same
individual. Efforts to develop such a national geneexpression
database are currently under way [44,45].
However, this national database approach will require
a better understanding of genome-wide gene
expression across the highly diverse human population
and of the effects of environmental factors
on this expression.