Gene expression profiles in normal human mammary epithelial cells (NHMECs) exposed to benzo(a)pyrene (BP) in the presence or absence of chlorophyllin.
John-K; Keshava-C; Richardson-DL; Weston-A; Nath-J
Environ Mol Mutagen 2007 Aug; 48(7):597
A panel of six NHMEC strains developed from breast tissue discarded at reduction mammoplasty was exposed to the ubiquitous carcinogen BP, both in the presence or absence of the chemopreventive agent chlorophyllin. Three exposure regimens were used: T1- solvent control (24h), T2- BP alone (24h), T3- 24h pretreatment with chlorophyllin followed by BP and chlorophyllin together (24h). Hu-Gene 133A arrays (Affymetrix, Santa Clara, CA) were used for expression analysis and the data analyzed using Microarray Suite 5.0 and Cluster and Tree View software. Genes altered by three fold or greater were considered for pathway analysis. Cross-talk among immune response genes were determined using Pathway Studio (Ariadne Genomics, Rockville, MD) and ArrayXPath software. A total of 49 genes were altered in T2 of which 43 were up-regulated and six down-regulated. A total of 125 genes were altered in T3 of which 103 were up-regulated and 22 down-regulated. The only gene up-regulated by more than three fold in all six cell strains was CYP1B1. Five immune response genes altered in T2 exhibited 2248 interactions involving a total of 1485 other genes. Twenty-four immune response genes altered in T3 exhibited 5782 interactions involving a total of 2299 other genes. Various immune response genes altered in T2 and T3 shared statistically significant associations (p < 0.05) with various pathways including: Biocarta, GenMAPP, PharmGKB and KEGG. These studies begin to define a role for carcinogen-induced immune response genes in human chemical carcinogenesis, and further suggest that the modulatory role of chlorophyllin in PAH mediated carcinogenesis may be mediated in part by interactions involving genes and pathways altered by BP exposure.
Analytical-methods; Analytical-processes; Cancer; Genes; Genetic-engineering; Genetic-factors; Immune-reaction; Statistical-analysis; Chemical-properties; Carcinogenesis; Carcinogens
Environmental and Molecular Mutagenesis; Special Issue: Abstracts from the Environmental Mutagen Society 38th Annual Meeting, October 20-24, 2007, Atlanta, Georgia