Gene expression profiling of human liver carcinoma (HepG2) cells exposed to the marine toxin okadaic acid

Lynne A Fieber, Justin B. Greer, Fujiang Guo, Douglas L Crawford, Kathleen S. Rein

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The marine toxin, okadaic acid (OA) is produced by dinoflagellates of the genera Prorocentrum and Dinophysis and is the causative agent of the syndrome known as diarrheic shellfish poisoning. In addition, OA acts as both a tumor promoter, attributed to OA-induced inhibition of protein phosphatases as well as an inducer of apoptosis. To better understand the potentially divergent toxicological profile of OA, the concentration-dependent cytotoxicity and alterations in gene expression on the human liver tumor cell line HepG2 upon OA exposure were determined using RNA microarrays, DNA fragmentation, and cell proliferation assays as well as determinations of cell detachment and cell death in different concentrations of OA. mRNA expression was quantified for approximately 15,000 genes. Cell attachment and proliferation were both negatively correlated with OA concentration. Detached cells displayed necrotic DNA signatures but apoptosis also was broadly observed. Data suggest that OA has a concentration dependent effect on cell cycle, which might explain the divergent effects that at low concentration OA stimulates genes involved in the cell cycle and at high concentrations it stimulates apoptosis.

Original languageEnglish
Pages (from-to)1805-1821
Number of pages17
JournalToxicological and Environmental Chemistry
Volume94
Issue number9
DOIs
StatePublished - Oct 1 2012

Fingerprint

Marine Toxins
Okadaic Acid
Hep G2 Cells
Gene Expression Profiling
Gene expression
Liver
toxin
gene expression
Carcinoma
Acids
acid
Cell death
apoptosis
Cells
Apoptosis
tumor
Tumors
Cell Cycle
DNA
Genes

Keywords

  • gene expression
  • HepG2
  • marine toxin
  • microarray
  • okadaic acid

ASJC Scopus subject areas

  • Environmental Chemistry
  • Health, Toxicology and Mutagenesis
  • Pollution

Cite this

Gene expression profiling of human liver carcinoma (HepG2) cells exposed to the marine toxin okadaic acid. / Fieber, Lynne A; Greer, Justin B.; Guo, Fujiang; Crawford, Douglas L; Rein, Kathleen S.

In: Toxicological and Environmental Chemistry, Vol. 94, No. 9, 01.10.2012, p. 1805-1821.

Research output: Contribution to journalArticle

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