Metabolism of benzo[a]pyrene by cultured human hepatocytes from multiple donors.
Metabolism of benzo[a]pyrene by cultured human hepatocytes from multiple donors.
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来自多个供体的培养人肝细胞对苯并[a]芘的代谢。
DOI：
10.1093/carcin/5.12.1577
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发表时间：
1984
期刊：
影响因子：
4.7
通讯作者：
Gould,MN
中科院分区：
文献类型：
--
作者：
Moore,CJ;Gould,MN
建立了来自六名人类捐赠者的原代肝细胞培养物，并检查了他们代谢多环芳烃致癌物苯并[a]芘（B[a]P）的能力。来自每个供体的细胞以相似的密度铺板（1 × 107 个细胞/100 mm 培养皿）。所有培养物均以显着程度代谢 B[a]P（24 小时内 24-35 nmol）并且 h.p.l.c.获得了所有供体的有机溶剂可溶性和葡萄糖醛酸化 B[a]P 代谢物的概况。主要的细胞外有机溶剂可溶性 B[a]P 代谢物是 9,10-和 7,8-二氢二醇、9-羟基-B[a]P 和四醇混合物，但这些代谢物的一般比例在不同供体的细胞中差异很大。相比之下，来自同一供体的细胞在初次铺板后 8 或 24 小时用 B[a]P 处理的情况具有高度可重复性。来自不同供体的细胞与葡萄糖醛酸缀合的特定 B[a]P 代谢物的量变化较小。这种变异性与细胞活力或 B[a]P 代谢的总体水平无关。此外，还比较了来自同一供体的新鲜肝细胞和冷冻保存的肝细胞的 B[a]P 代谢。虽然细胞冷冻后总 B[a]P 代谢水平仅小幅下降，但冷冻预缝合测试的细胞在细胞外培养基和葡萄糖醛酸缀合物中发现的 B[a]P-7,8 二氢二醇产量增加了 3 至 5 倍。
Primary hepatocyte cultures from six human donors were established and their abilities to metabolize the polycyclic aromatic hydrocarbon carcinogen benzo[a]pyrene (B[a]P) were examined. Cells from each donor were plated at similar densities (1 × 107cells/100 mm dish). All cultures metabolized B[a]P to a significant extent (24–35 nmol in 24 h) and h.p.l.c. profiles of the organic solvent-soluble and glucuronidated B[a]P metabolites were obtained for all donors. The predominant extracellular organic solvent-soluble B[a]P metabolites were the 9,l0- and 7,8-dihydrodiols, 9-hydroxy-B[a]P, and a mixture of tetrols, but the general ratios of these metabolites varied widely among the cells from different donors. In contrast, profiles were highly reproducible in cells from the same donor treated with B[a]P at either 8 or 24 h after initial plating. There was less variability in the amounts of specific B[a]P metabolites conjugated to glucuronic acid by cells from various donors. This variability could not be correlated with cell viability or overall levels of B[a]P metabolism. In addition, B[a]P metabolism by fresh and cryopreserved hepatocytes from the same donor was compared. While there was only a small reduction in the level of total B[a]P metabolism after cell freezing, there was a 3- to 5-fold increase in production of B[a]P-7,8dihydrodiol, found both in the extracellular medium and as glucuronic acid conjugates, by the cryopresewed cells tested.