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首页> 外文期刊>Mutation research. Genetic toxicology testing >INCREASED GENOTOXICITY OF ACETYLAMINOFLUORENE BY MODULATORS OF MULTIXENOBIOTIC RESISTANCE MECHANISM - STUDIES WITH THE FRESH WATER CLAM CORBICULA FLUMINEA
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INCREASED GENOTOXICITY OF ACETYLAMINOFLUORENE BY MODULATORS OF MULTIXENOBIOTIC RESISTANCE MECHANISM - STUDIES WITH THE FRESH WATER CLAM CORBICULA FLUMINEA

机译：多种抗异肠机制的调节剂增强乙酰氟的遗传毒性-淡水包岩藻的研究。

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The presence of a 'multixenobiotic resistance' [MXR] mechanism in gills of the freshwater clam Corbicula fluminea was investigated. Western blot analyses of membrane vesicles from gills, applying antibodies to vertebrate P170 multidrug resistance (MDR) protein, revealed a 135 kDa immunoreactive protein. Verapamil caused a reduction of H-3-vincristine (H-3-VCR) binding onto vesicles from clam. Exposure of clams to H-3-VCR in the presence of verapamil or staurosporine (STP) enhanced the accumulation of H-3-VCR over control values. Furthermore, clams were exposed instead to VCR, to a model carcinogen, 2-acetylaminofluorene (AAF), to determine the verapamil- and STP-dependent increase of single-strand breaks (SSBs) in DNA from gills of this organism. Verapamil caused no or little increase of SSBs induced by exposure to 0.01 or 0.10 mu M AAF, respectively, as measured by the alkaline elution technique. In contrast, in the presence of STP a highly significant and dose-dependent enhancement of AAF-mediated SSBs was measured already at exposure to 0.01 mu M AAF. These data indicate (i) that the clam C. fluminea is provided with a P-glycoprotein-like element of the MDR-mechanism, (ii) that this system can be poisoned by chemosensitizers such as verapamil and STP, (iii) the role of protein kinase C in the regulation of MXR function and (iv) the importance of the MXR modulators for the assessment of ecotoxicological effects of pollutants.
机译：研究了淡水蛤Cor（Corbicula fluminea）g中“多重异生抗药性” [MXR]机制的存在。对vertebrate的膜囊泡进行Western blot分析，将抗体应用于脊椎动物P170多药抗性（MDR）蛋白，发现了135 kDa的免疫反应蛋白。维拉帕米引起​​H-3-长春新碱（H-3-VCR）与蛤lam囊泡结合的减少。在维拉帕米或星形孢菌素（STP）存在下，将蛤暴露于H-3-VCR会增加H-3-VCR的积累，超过控制值。此外，将蛤代替VCR暴露于模型致癌物2-乙酰氨基芴（AAF），以确定该生物g中DNA的维拉帕米和STP依赖性单链断裂（SSB）依赖性增加。用碱性洗脱技术测得，维拉帕米分别引起0.01或0.10μM AAF诱导的SSB升高，几乎没有或几乎没有升高。相反，在存在STP的情况下，在暴露于0.01μMAAF时已经测量到AAF介导的SSB的高度显着且剂量依赖性增强。这些数据表明（i）蛤C梭状芽胞杆菌具有MDR机制的P-糖蛋白样元件，（ii）该系统可被化学敏化剂（如维拉帕米和STP）中毒，（iii）作用蛋白激酶C在MXR功能调节中的作用;以及（iv）MXR调节剂对于评估污染物的生态毒理学作用的重要性。

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