Abstracts: ISEE 22nd Annual Conference, Seoul, Korea, 28 August-1 September 2010: Exposure Assessment by Various Media and Pathways
The chemical composition of the persistent organic pollutants (POP) contains many structurally different lipophilic compounds with distinctive toxicogenomic properties. The extensive works on PCB indicated that the composite effect is entirely different from the effect of the individual PCB congeners studied in vitro, and may be synergistic or antagonistic in nature. Our differential gene expression work in evaluating the POP-related toxicities on human being may help to understand the composite effect of the exposure as a collective entity.
The exposed Slovakian children (mean age, 45 month) were placed in high (>75% tile,) and low (<25% tile) prevalent POP groups, on the basis of blood concentration of POPs including polychlorinated biphenyls, 2,2′-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), 2,2′-bis(4-chlorophenyl)-1,1,1-trichloro-ethane p,p-DDT), hexachlorobenzene, and β-hexachlorocyclohexane (β-HCH). The microarray studies were performed on Affymetrix platform (GeneChip Human genome U133 Plus 2.0 Array) using RNA from peripheral blood mononuclear cells of the children. The qRT-PCR method was used to validate differential gene expression. The global gene expressions in children of high- and low-POP exposure groups were compared by GeneSpring GX10.
The significant set of differentially expressed genes was analyzed using Ingenuity Pathway Analysis. The mostly affected network functions are cell cycle, cancer, genetic disorder lipid metabolism, small molecule biochemistry, drug metabolism, etc, and the top Tox list included anti-apoptosis, fatty acid metabolism, p53 signaling phenomenon; in higher POP exposure. The incidence of cancer and the metabolic impairments is often reported pathophysiologically in epidemiological studies.
The gene expressions profile provided the molecular mechanism of POP-related toxicities. The future gene expression data from populations exposed to POPs of different chemical profiles are highly essential to understand the complex nature of this collective injury on human health.