Aflatoxin toxicity in cultured human epidermal cells: stimulation by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Aflatoxin toxicity in cultured human epidermal cells: stimulation by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
复制标题
黄曲霉毒素对培养的人表皮细胞的毒性：2,3,7,8-四氯二苯并-对二恶英的刺激。
DOI：
10.1093/carcin/13.11.2029
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发表时间：
1992
期刊：
影响因子：
4.7
通讯作者：
Rice,RH
中科院分区：
文献类型：
--
作者：
Walsh,AA;Hsieh,DP;Rice,RH
1 μg/ml 的黄曲霉毒素 B1(AFB1) 对 Rheinwald-Green 3T3 饲养层系统中生长的人表皮细胞具有显着毒性。根据暴露 2 周期间的菌落扩增评估，在 0.1 μg/ml 浓度下，毒性几乎不明显，但 5 nM 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 会显着刺激毒性，而单独使用时是无毒的。在存在或不存在 TCDD 的情况下，AFB1-二氢二醇和 AFB2 均无毒性，表明代谢为 8,9-环氧化物是造成 AFB1 毒性的原因。与单独的 AFB1 相比，暴露于 [14C]AFB1 和 TCDD 4 天的培养物中 DNA 加合物形成增加了 20 倍以上，这也表明 TCDD 对 AFB1 环氧化的刺激。通过反相 HPLC 对培养基中游离代谢物的分析表明，汇合的表皮培养物将 AFB1 代谢为 AFM1、AFB2a 和黄曲霉毒素。在存在 TCDD 的情况下，AFM1 的水平较高（剂量的 14% 对 3%），AFB2a 的水平也较高（剂量的 3% 对 0.5%），而黄曲霉毒素水平较低（剂量的 0.8% 对 2%）。在没有辐照3T3的情况下，AFB1、AFB2、AFM1和黄曲霉酚对无血清培养基（0.15 mM Ca2+）中细胞的毒性与饲养层系统中的毒性相似。尽管这种适度低的钙浓度对于观察毒性来说似乎相当令人满意，但在较低的钙浓度（0.09 mM Ca2+）下反应减弱。
Aflatoxin B1(AFB1) at 1 μg/ml was markedly toxic to human epidermal cells grown in the Rheinwald-Green 3T3 feeder layer system. At 0.1 μg/ml, the toxicity was barely evident, as assessed by colony expansion during a 2 week exposure, but it was dramatically stimulated by 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which was non-toxic alone. Neither AFB1-dihydrodiol nor AFB2were toxic in the presence or absence of TCDD, indicating that metabolism to the 8,9-epoxide was responsible for the AFB1toxicity. Stimulation of AFB1epoxidation by TCDD was also indicated by the >20-fold increase in DNA adduct formation in cultures exposed to [14C]AFB1and TCDD for 4 days as compared to AFB1alone. Analysis of free metabolites in culture medium by reverse-phase HPLC revealed that confluent epidermal cultures metabolized AFB1to AFM1, AFB2aand aflatoxicol. In the presence of TCDD, the levels of AFM1were higher (14 versus 3% of dose) as were those of AFB2a(3 versus 0.5% of dose), while aflatoxicol levels were lower (0.8 versus 2% of dose). In the absence of irradiated 3T3, the toxicities of AFB1, AFB2, AFM1and aflatoxicol to cells in serum-free medium (0.15 mM Ca2+) were similar to those in the feeder layer system. Although this moderately low calcium concentration appeared quite satisfactory for observing toxicity, the response was attenuated at a lower calcium concentration (0.09 mM Ca2+).