Immune response signatures of benzo{alpha}pyrene exposure in normal human mammary epithelial cells in the absence or presence of chlorophyllin.
Carcinogenic polycylic aromatic hydrocarbons can alter immune responses. Changes in immune response gene expression profiles in multiple human mammary cell strains exposed to benzo(alpha)pyrene (BP) (4 microM) in vitro, in the presence or absence of chlorophyllin (5 microM), were observed using Affymetrix gene arrays. Expressions of five immune response genes were altered ~3.0-fold by BP exposure and 24 genes by BP in the presence chlorophyllin. In silico pathway analysis revealed altered immune response genes form interactive gene networks with many cellular processes, suggesting their role in a complex multigenic response to toxins. Additionally, it was suggestive of the possible immunomodulatory potential of chlorophyllin apart from various other well-documented mechanisms of action. Gene expression matrices revealed consistent alteration patterns involving IL1B, SECTM1 and CXCL14 on exposure to BP, and IL1RN, CD86, IF144 and GIP2 in the presence of chlorophyllin and BP, suggesting some of these genes might constitute putative immune response biomarkers of PAH exposure. This study has therefore identified a battery of potential immune response biomarkers of PAH exposure, amidst several genes, for future validation studies.
John
Kaarthik
K
Genetics and Developmental Biology Program, 1120 Agricultural Sciences Building, West Virginia University, Morgantown, WV26506-6108, USA.
Keshava
Channa
C
Richardson
Diana L
DL
Weston
Ainsley
A
Nath
Joginder
J
D016587:Antimutagenic Agents / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism*; D002478:Cells, Cultured; D002735:Chlorophyllides / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016587:Antimutagenic Agents; D015415:Biomarkers; D002735:Chlorophyllides; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D001564:Benzo(a)pyrene; C007020:chlorophyllin