GENE EXPRESSION PROFILING OF HUMAN LIVER CARCINOMA (HepG2) CELLS EXPOSED TO THE MARINE TOXIN OKADAIC ACID.

IF 1.1 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES
Lynne A Fieber, Justin B Greer, Fujiang Guo, Douglas C Crawford, Kathleen S Rein
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引用次数: 7

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 (DSP). 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.

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)是由原心藻属和甲藻属的鞭毛藻产生的,是腹泻性贝类中毒(DSP)综合征的病原体。此外,OA作为肿瘤启动子(由于OA诱导蛋白磷酸酶的抑制)和细胞凋亡的诱导剂。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、细胞增殖试验以及不同浓度OA下细胞脱离和细胞死亡的测定,测定了OA暴露后人肝肿瘤细胞系HepG2的浓度依赖性细胞毒性和基因表达的变化。大约15,000个基因的mRNA表达量被量化。细胞附着和增殖均与OA浓度呈负相关。分离细胞显示坏死的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,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作用。
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来源期刊
Toxicological and Environmental Chemistry
Toxicological and Environmental Chemistry ENVIRONMENTAL SCIENCES-TOXICOLOGY
CiteScore
3.50
自引率
5.60%
发文量
0
期刊介绍: The journal is interdisciplinary in outlook, and manuscripts published in it cover all relevant areas: • inorganic chemistry – trace elements in food and the environment, metal complexes and chelates; • organic chemistry – environmental fate, chemical reactions, metabolites and secondary products, synthesis of standards and labelled materials; • physical chemistry – photochemistry, radiochemistry; • environmental chemistry – sources, fate, and sinks of xenochemicals, environmental partitioning and transport, degradation and deposition; • analytical chemistry – development and optimisation of analytical methods, instrumental and methodological advances, miniaturisation and automation; • biological chemistry – pharmacology and toxicology, uptake, metabolism, disposition of xenochemicals, structure-activity relationships, modes of action, ecotoxicological testing.
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