title: Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water.
abstract: 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.
authors.affiliation: 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.
authors.forename: Mayuko Y
authors.initials: MY
authors.lastname: Kumasaka
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanoshita
authors.forename: Shingo
authors.initials: S
authors.lastname: Shimizu
authors.forename: Shoko
authors.initials: S
authors.lastname: Ohnuma
authors.forename: Akio
authors.initials: A
authors.lastname: Furuta
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yajima
authors.forename: Saika
authors.initials: S
authors.lastname: Nizam
authors.forename: Md
authors.initials: M
authors.lastname: Khalequzzaman
authors.forename: Hossain U
authors.initials: HU
authors.lastname: Shekhar
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
mesh_terms: D000327:Adsorption; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D018053:Arsenites / Q000633:toxicity*; D001459:Bangladesh; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002614:Chelating Agents / Q000494:pharmacology*; D060766:Drinking Water / Q000009:adverse effects* / Q000032:analysis; D004357:Drug Synergism; D004784:Environmental Monitoring; D052918:Environmental Restoration and Remediation / Q000379:methods*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D058085:Iron Compounds / Q000032:analysis / Q000633:toxicity*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008276:Magnesium Hydroxide / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D017670:Sodium Compounds / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D018053:Arsenites; D002614:Chelating Agents; D060766:Drinking Water; D058085:Iron Compounds; D017670:Sodium Compounds; D014874:Water Pollutants, Chemical; C010467:hydrotalcite; C017947:sodium arsenite; D000536:Aluminum Hydroxide; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D008276:Magnesium Hydroxide