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.

中文翻译：

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暴露于海洋毒素冈田酸的人肝癌 (HepG2) 细胞的基因表达谱

海洋毒素冈田酸 (OA) 由 Prorocentrum 和 Dinophysis 属的鞭毛藻产生，是称为腹泻性贝类中毒综合征的病原体。此外，OA 既是肿瘤促进剂，归因于 OA 诱导的蛋白磷酸酶抑制以及细胞凋亡的诱导剂。为了更好地了解 OA 潜在的不同毒理学特征，使用 RNA 微阵列、DNA 片段化和细胞增殖测定以及测定不同浓度OA下的细胞脱离和细胞死亡。对大约 15,000 个基因的 mRNA 表达进行了量化。细胞附着和增殖均与 OA 浓度呈负相关。分离的细胞显示出坏死的 DNA 特征，但也广泛观察到细胞凋亡。数据表明 OA 对细胞周期具有浓度依赖性影响，这可能解释了低浓度 OA 刺激参与细胞周期的基因和高浓度 OA 刺激细胞凋亡的不同效应。