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Altered gene expression in response to diesel exhaust particulate matter (SRM 1650a) in MCF-7 cells detected with DNA microarrays.

Authors
Mahadevan-B; Keshava-C; Brooks-E; Weston-A; Baird-WM
Source
97th AACR Annual Meeting, April 1-5, 2006, Washington D.C. Philadelphia, PA: American Association for Cancer Research, 2006 Apr; 47:5207
NIOSHTIC No.
20029959
Abstract
Human exposures to polycyclic aromatic hydrocarbons (PAHs) occurs in the form of complex mixtures. Some of these PAHs are carcinogenic. Standard Reference Material (SRM) 1650a-Diesel particulate matter was determined by the National Institute of Standards and Technology to contain a mixture of specific PAHs and nitro-substituted PAHs. In this study the gene expression patterns were investigated in MCF-7 cells (derived from a human mammary carcinoma) exposed (24h) to SRM 1650a alone or in combination with the carcinogenic PAH benzo[a]pyrene (BP) or dibenzo[a,l]pyrene (DBP). Gene expression was monitored using high density oligonucleotide arrays (Affymetrix U I33A). Exposure of MCF-7 cells to SRM 1650a alone or in combination with BP or DBP resulted in altered gene expression patterns of many RNA species. The data reported here were based on 2-fold up-regulation or down-regulation of genes that were statistically significant (p = 0.05). Global gene expression analysis revealed 30, 127 and 19 genes that were significantly altered in response to SRM 1650a, SRM 1650a plus BP, or DBP, respectively. Functional classification of differentially expressed genes indicated that several of the genes were either directly or indirectly involved in metabolism of PAHs, cell cycle regulation, proliferation, DNA repair and tumor suppression. In a previous study we have shown that CYP1A1 and CYP1B1 were up-regulated on exposure to BP (Cancer Research, 2005, 65:1251-58). In this study, an induction of the same genes was noticed on co-treatment with SRM 1650a plus BP. Unlike SRM 1650a alone or co-treatment with BP, expression of CYP1A1 was not observed when the cells were co-treated with SRM 1650a and DBP, although expression of CYP1B1 was evident. These results not only provide a transcriptional signature to chemical carcinogen exposure, but also assist in the development of specific and sensitive biomarkers for use in studies of exposure and susceptibility, both in mechanistic and epidemiological studies.
Keywords
Diesel-exhausts; Particulates; Polycyclic-aromatic-hydrocarbons; Carcinogens; Carcinogenicity; Carcinogenesis; Exposure-levels; Exposure-assessment; Genes
CAS No.
50-32-8; 189-55-9
Publication Date
20060401
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
2006
NTIS Accession No.
NTIS Price
ISSN
0197-016X
NIOSH Division
DRDS; HELD
Source Name
97th American Association for Cancer Research Annual Meeting, April 1-5, 2006, Washington D.C.
State
WV; OR; DC
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