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Effects of indomethacin and arachidonic acid on sister chromatid exchange induction by styrene and styrene-7,8-oxide

机译:消炎痛和花生四烯酸对苯乙烯和7,8-苯乙烯氧化物诱导姊妹染色单体交换的影响

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摘要

Styrene is converted into styrene-7,8-oxide in human lymphocyte cultures, in a reaction probably mediated by oxyhemoglobin. As a consequence, styrene induces sister-chromatid exchanges (SCEs) in whole-blood lymphocyte cultures without exogenous metabolic activation systems. Another metabolic pathway that could be involved in the metabolism of styrene is cooxidation by prostaglandin-endoperoidde synthase (PES). To study the role ofPES in the metabolism of styrene, human whole-Wood lymphocyte cultureswere treated for the entire culture time of 72-h with styrene (0.5 and 1 mM) or styrene-7,8-oxide (50 and 100 muM), in. the presence and absence of 75 or 150 muM indometh'a'cin Can inhibitor of PES) and arachidonic acid (substrate of PES). Indomethacin potentiated SCE induction by both styrene and styrene-7,8-oxide; a slight but statistically significant enhancement (16-32%; p < 0.05 - p < 0.001) was observed in all treatments with styrene and at 150 /muM indomethacin in the case of styrene-7,8-oxide. At 150 M, ,arElchidonic iacid induced a 15-20% suppression (p < 0.01) in SCE induction by both slyrene (1 mM only) and Styrene-7,8-oxide (100 /muM only). Indomethacin or arachidonic acid did not alone influence the frequency of SOEs. The- results -Suggest that PES acts as an inactivation route for styrene and styrene-7,8-oxide in human whole-blood lymphocyte cultures, possibly through PES-mediated binding to glutathione.
机译:在可能由氧合血红蛋白介导的反应中,苯乙烯在人淋巴细胞培养物中转化为苯乙烯-7,8-氧化物。结果,苯乙烯在没有外源性代谢活化系统的全血淋巴细胞培养物中诱导姐妹染色单体交换(SCE)。可能与苯乙烯代谢有关的另一种代谢途径是前列腺素-内胚层合酶(PES)的共氧化作用。为了研究PES在苯乙烯代谢中的作用,将人类全木淋巴细胞培养物在72小时的整个培养时间内用苯乙烯(0.5和1 mM)或苯乙烯7,8-氧化物(50和100μM)处理,存在或不存在75或150μM的吲哚美辛可以抑制PES)和花生四烯酸(PES的底物)。消炎痛增强了苯乙烯和7,8-苯乙烯氧化物对SCE的诱导作用;在所有用苯乙烯和在吲哚美辛为150 /μM的吲哚美辛中处理的所有苯乙烯处理中,均观察到轻微但统计学上显着的增强(16-32%; p <0.05-p <0.001),对于苯乙烯7,8-氧化物。在150 / nM时,arlychidonic iacid通过slyrene(仅1 mM)和苯乙烯7,8-氧化物(仅100 /μM)诱导SCE诱导抑制15-20%(p <0.01)。消炎痛或花生四烯酸并不单独影响国有企业的出现频率。结果表明,PES可能是人类全血淋巴细胞培养物中苯乙烯和7,8-苯乙烯氧化物的失活途径,可能是通过PES介导的与谷胱甘肽的结合。

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