Units of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto-cho, Kasugai-shi, Aichi, 487-8501, Japan.
Arch Toxicol. 2013 Mar;87(3):439-47. doi: 10.1007/s00204-012-0964-6. Epub 2012 Oct 26.
Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic-polluted well water, especially in Bangladesh. Although well drinking water in the cancer-prone areas contains various elements, very little is known about the effects of elements except arsenic on carcinogenicity. In order to clarify the carcinogenic effects of coexposure to arsenic and iron, anchorage-independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined. Since the mean ratio of arsenic and iron in well water was 1:10 in cancer-prone areas of Bangladesh, effects of 1 μM arsenic and 10 μM iron were investigated. Iron synergistically promoted arsenic-mediated anchorage-independent growth in untransformed and transformed keratinocytes. Iron additionally increased invasion in both types of keratinocytes. Activities of c-SRC and ERK that regulate anchorage-independent growth and invasion were synergistically enhanced in both types of keratinocytes. Our results suggest that iron promotes arsenic-mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes. We then developed a low-cost and high-performance adsorbent composed of a hydrotalcite-like compound for arsenic and iron. The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer-prone areas of Bangladesh to levels less than those in WHO health-based guidelines for drinking water. Thus, we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water.
包括皮肤癌在内的各种癌症在饮用砷污染井水的砷中毒患者中呈爆炸式增长，尤其是在孟加拉国。尽管癌症高发地区的井水含有多种元素，但除砷以外，对其他元素的致癌性知之甚少。为了阐明砷和铁共同暴露的致癌作用，我们检测了人未转化 HaCaT 和转化 A431 角质细胞的无锚定生长和侵袭。由于孟加拉国癌症高发地区井水中砷和铁的平均比值为 1:10，因此研究了 1 μM 砷和 10 μM 铁的作用。铁协同促进未转化和转化角质细胞中砷介导的无锚定生长。铁还额外增加了两种角质细胞的侵袭。调节无锚定生长和侵袭的 c-SRC 和 ERK 活性在两种角质细胞中协同增强。我们的结果表明，铁促进了未转化角质细胞中砷介导的转化和转化角质细胞的进展。然后，我们开发了一种由水滑石类似物组成的低成本、高性能吸附剂，用于砷和铁。该吸附剂可迅速将孟加拉国癌症高发地区井水的两种元素浓度降低到低于世界卫生组织饮用水健康基准值的水平。因此，我们不仅首次证明了砷和铁共同暴露会增加致癌性，还提出了一种用于井水修复的新型处理系统。
