Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA.
Toxicol Sci. 2013 Aug;134(2):271-5. doi: 10.1093/toxsci/kft120. Epub 2013 Jun 6.
Intramitochondrial inclusions containing arsenite that occur within urothelial cells have been previously described in mice exposed to high concentrations of arsenic but not in rats. In epidemiology studies, similar urothelial cell inclusions have also been observed in the urine of humans exposed to high concentrations of arsenic in the drinking water; however, these inclusions were mistakenly identified as micronuclei. To further examine the urothelial cell inclusions that occur in inorganic arsenic-exposed humans, we evaluated two patients with a history of acute promyelocytic leukemia treated for disease relapse with a combination of all-trans retinoic acid and arsenic trioxide. Posttreatment examination of the patients' urine cytology specimens by light and electron microscopy demonstrated cytoplasmic inclusions in exfoliated superficial urothelial cells similar to those seen in mice. The inclusions were present in decreasing quantities at 3 and 7 months after completion of treatment. No comparable inclusions were detected in exfoliated urothelial cells in urine from six individuals not treated with arsenic trioxide. Based on the results of the examination by light and electron microscopy, we have determined that urothelial cell inclusions in the urine of humans previously identified as micronuclei are instead intracytoplasmic inclusions similar to those found in arsenic-treated mice.
先前曾在暴露于高浓度砷的小鼠的尿路上皮细胞中描述过含有亚砷酸盐的线粒体内含物，但在大鼠中未发现。在流行病学研究中，在饮用水中暴露于高浓度砷的人类尿液中也观察到了类似的尿路上皮细胞内含物；然而，这些内含物被错误地鉴定为微核。为了进一步研究无机砷暴露的人类中发生的尿路上皮细胞内含物，我们评估了两名有急性早幼粒细胞白血病病史的患者，他们因疾病复发而接受全反式维甲酸和三氧化二砷联合治疗。通过光镜和电子显微镜对患者治疗后尿液细胞学标本进行检查，结果显示脱落的浅层尿路上皮细胞中存在细胞质内含物，与在小鼠中观察到的内含物相似。在治疗完成后 3 个月和 7 个月时，内含物的数量减少。在未用三氧化二砷治疗的 6 名个体的尿液脱落尿路上皮细胞中未检测到类似的内含物。基于光镜和电子显微镜检查的结果，我们确定先前被鉴定为微核的人类尿液中的尿路上皮细胞内含物实际上是类似于在砷处理的小鼠中发现的细胞内内含物。
