title: Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B1.
abstract: Aflatoxin B1 (AFB1) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB1-DNA adducts in AFB1-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB1 and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4h after AFB1 administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB1-induced hepatotoxicity. At 24h after AFB1 administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB1-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB1 hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer.
authors.affiliation: Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210, Thailand.
authors.forename: Nirachara
authors.initials: N
authors.lastname: Techapiesancharoenkij
authors.affiliation: Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jeannette L A
authors.initials: JL
authors.lastname: Fiala
authors.affiliation: Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210, Thailand.
authors.forename: Panida
authors.initials: P
authors.lastname: Navasumrit
authors.affiliation: Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Croy
authors.affiliation: Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Gerald N
authors.initials: GN
authors.lastname: Wogan
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Groopman
authors.affiliation: Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210, Thailand.
authors.forename: Mathuros
authors.initials: M
authors.lastname: Ruchirawat
authors.affiliation: Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: jessig@mit.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Essigmann
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D019610:Cytoprotection; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D017879:Isothiocyanates / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008563:Membrane Lipids / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013454:Sulfoxides; D013997:Time Factors
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D008563:Membrane Lipids; D012333:RNA, Messenger; D013454:Sulfoxides; D016604:Aflatoxin B1; C016766:sulforaphane
keywords: Aflatoxin B(1); Chemoprevention; Gene expression profiling; Membrane biosynthesis; Sulforaphane