Transcriptional profiles of benzo(a)pyrene exposure in normal human mammary epithelial cells in the absence or presence of chlorophyllin.
John K; Keshava C; Richardson DL; Weston A; Nath J
Mutat Res Fundam Mol Mech Mutagen 2008 Apr; 640(1-2):145-152
Benzo(a)pyrene (BP) exposure causes alterations in gene expression in normal human mammary epithelial cells (NHMECs). This study used Affymetrix Hu-Gene133A arrays, with 14,500 genes represented, to evaluate modulation of BP-induced gene expression by chlorophyllin in six NHMEC strains derived from different donors. A major goal was to seek potential biomarkers of carcinogen exposure and how they behave in the presence of a chemopreventive agent. NHMECs (passage 6 and 70% confluence) were exposed for 24 h to either vehicle control, or BP or chlorophyllin followed by BP and chlorophyllin together. BP exposure resulted in approximately 3-fold altered expression of 49 genes in at least one of the six NHMEC strains. When cells were exposed to chlorophyllin pre-treatment followed by BP plus chlorophyllin, expression of 125 genes was similarly altered. Genes in the functional categories of xenobiotic metabolism, cell signaling, cell motility, cell proliferation, cellular transcription, metabolism, cell cycle control, apoptosis and DNA repair were identified. Only CYPIBI and ALDHIA3 were consistently up-regulated by similar to 3-fold in most of the cell strains (at least 4) when exposed to BP. Cluster analysis identified a suite of 13 genes induced by BP where induction was mitigated in the presence of chlorophyllin. Additionally, cluster analysis identified a suite of 16 genes down-regulated by BP where induction was partially restored in the presence of chlorophyllin.
Histopathology; Immunotoxins; Immune-reaction; Immune-system; Cell-biology; Cell-differentiation; Cell-function; Cell-metabolism; Cell-transformation; Cellular-reactions; Cellular-transport-mechanism; Biological-effects; Biological-monitoring; Biomarkers; Carcinogenicity; Genes; Genetic-factors; Genetics; Genotoxicity; Humans; Mammalian-cells;
Author keywords: Carcinogens; Chemoprevention; Chlorophyllin; Gene expression; Polycyclic aromatic hydration
Joginder Nath, Genetics and Developmental Biology Program, 1120 Agricultural Sciences Building, West Virginia University, Morgantown, WV 26506-6108
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis