A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins alpha 1-microglobulin and glutathione-S-transferase alpha (GST alpha) as biomarkers for damage of the proximal tubule and glutathione-S-transferase pi (GST pi) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers alpha 1-microglobulin, GST alpha, and GST pi consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

译文

:对前德意志民主共和国铜矿开采行业中高度暴露于二硝基甲苯(DNT)的161名地下矿工进行了重新研究,以寻找亚临床肾脏损害的迹象。该研究包括通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)排泄的尿蛋白的筛查,以及定量特定尿蛋白α1-微球蛋白和谷胱甘肽-S-转移酶α(GSTα)的生物标志物,以检测尿液的损害。远端小管和谷胱甘肽-S-转移酶pi(GST pi)用于远端小管的损伤。根据与DNT专业接触的类型和持续时间,将暴露量半定量分类(低,中,高和非常高)。观察到病理蛋白排泄模式与DNT暴露的半定量排名具有直接的剂量依赖性。先前报道的大多数泌尿道癌症病例,尤其是那些暴露程度较高的人群,都局限于病理性尿蛋白排泄模式。 DNT的损害直接指向了管状系统。在许多情况下,注意到出现了Tamm-Horsfall蛋白(105 kD蛋白标记)的出现。有关生物标志物α1-微球蛋白,GSTα和GST pi的数据始终表明肾小管损伤呈剂量依赖性增加,这证实了SDS-PAGE筛选的结果,并明确表明在给定的暴露条件下DNT的肾毒性作用。在暴露于DNT的工人中观察到的癌症患者群体中,仅在例外情况下才发现正常的生物标志物排泄物。

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