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Advisory Committee on Health Effects of Endocrine Disruptors
The Supplement II to the Intermediary Report
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(4) Endocrine disruptor study using genomic techniques
Identification of gene profiles which serve as biomarkers has
achieved considerable advance. A further step to biomarker
identification based on proteomics will be advantageous for
administrative purposes58.
Candidate approaches are developing of a chip specifically
designed for markers of possible problems caused by endocrine
disruptors59, or regarding gene
expression as a phenotype (reverse science)60.
Each of these approaches has advantages according to
applications. The following problems should also be taken into
account.
- Possibility of long-term prediction from effects initially
observed
- Adequate approach to dose-effect relationship, dose-specific
gene profiling
- Possibility of prediction of combined effects (for which they
will be useful)
- Possibility of extrapolation to different animal species
(gene profiling concerning homologous phenotype)
- Correlation between the gene expressions in cells and tissues
in vitro and in individuals61
A considerable part of these topics overlap the low-dose issue.
Along with genomics, informatics is considered to play an
important role in future studies. Introduction of these "omics"
techniques was discussed in a WHO/IPCS workshop in Berlin62
and an OECD workshop in Kyoto63
to identify major technical problems.
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58 Watanabe H, Suzuki A, Mizutani T, Kohno
S, Lubahn DB, Handa H, Iguchi. Genome-wide analysis of changes
in early gene expression induced by estrogen. Genes Cells, 7:
497-507, 2002.
59 ChineChipTM Probe Array Technology, Copyrihgt 2000,
Affymetrix, Inc.
60 T. Inoue & W.D.Pennie (eds) Toxicogenomics. Springer,
Tokyo, Berlin 2003, pp.3-11.
61 Inoue T, Igarashi K, Sekizawa J. JMAJ (Japan Medical
Association Journal) 46: 97-102, 2003.
62 Held at the Federal Institute for
Risk Assessment, Berlin, Nov. 17-19, 2003, Proceedings in press
63 Held at Kyoto International
Conference Center, Oct. 13-15, 2004, Proceedings in press |
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