Transcriptional profiles of benzo(a)pyrene exposure in normal human mammary epithelial cells in the absence or presence of chlorophyllin.
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 24h 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 CYP1B1 and ALDH1A3 were consistently up-regulated by approximately 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.
John
Kaarthik
K
Genetics and Developmental Biology Program, 1120 Agricultural Sciences Building, West Virginia University, Morgantown, WV 26506-6108, United States.
Keshava
Channa
C
Richardson
Diana L
DL
Weston
Ainsley
A
Nath
Joginder
J
D001564:Benzo(a)pyrene / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D002735:Chlorophyllides / Q000494:pharmacology*; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D042361:Mammary Glands, Human / Q000187:drug effects*; D009153:Mutagens / Q000633:toxicity*; D014158:Transcription, Genetic
D015415:Biomarkers; D002735:Chlorophyllides; D009153:Mutagens; D001564:Benzo(a)pyrene; C007020:chlorophyllin