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Author Techapiesancharoenkij, Nirachara ♦ Fiala, Jeannette L. A. ♦ Navasumrit, Panida ♦ Croy, Robert G. ♦ Wogan, Gerald N. ♦ Groopman, John D. ♦ Ruchirawat, Mathuros ♦ Essigmann, John M.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ AFLATOXINS ♦ ANIMAL TISSUES ♦ BIOSYNTHESIS ♦ CARBOXYLIC ACIDS ♦ CELL PROLIFERATION ♦ DNA ADDUCTS ♦ GENE REGULATION ♦ GENES ♦ GLUTATHIONE ♦ GLYCOLYSIS ♦ LIVER ♦ MALES ♦ MEMBRANES ♦ NEOPLASMS ♦ PLANT GROWTH ♦ RATS ♦ TRANSFERASES ♦ VEGETABLES
Abstract Aflatoxin B{sub 1} (AFB{sub 1}) 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 AFB{sub 1}-DNA adducts in AFB{sub 1}-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 AFB{sub 1} and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB{sub 1} administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB{sub 1}-induced hepatotoxicity. At 24 h after AFB{sub 1} administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB{sub 1}-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 AFB{sub 1} hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer. - Highlights: • This study revealed sulforaphane (SF)-deregulated gene sets in aflatoxin B{sub 1} (AFB{sub 1})-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB{sub 1}-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-01-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 282
Issue Number 1


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