The elucidative research of the factors which regulate the symptoms of chronic arsenic poisoning

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15406022
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Hygiene
• Research Institution: Asahikawa Medical College
• Principal Investigator: YOSHIDA Takahiko Asahikawa Medical College, Professor, 医学部, 教授 (90200998)
• Co-Investigator(Kenkyū-buntansha): ITOH Toshihiro Asahikawa Medical College, Assistant Professor, 医学部, 講師 (20271760) ; NAKAGI Yoshihiko Asahikawa Medical College, Assistant, 医学部, 助手 (90322908) ; YAMAUCHI Hiroshi St.Marianna Medical College, Associate Professor, 医学部, 助教授 (90081661)
• Project Period (FY): 2003 – 2004
• Keywords: arsenic poisoning / drinking water / hyperkeratosis of skin / dyspigmentation of skin / methylation / epidermal keratinocyte / dermal fibroblast / gender difference

Research Abstract

We examined the relation between arsenic exposure and skin lesions in the residents who had been lived at naturally arsenic contaminated field and had been exposed to arsenic at various dose via drinking well water in Baotou county of Inner Mongolia, China. Odds ratio in prevalence of skin lesions especially of dyspigmentation was significantly higher in male residents. Ability to methylate arsenic ; 1st or 2nd methylation, estimated by measuring arsenic concentration with their chemical types in blood or urine from individual subjects was studied as being related to their skin lesions. Male showed lower ability of 2nd methylation compare with female. The cases with higher ability of 1st methylation and lower ability of 2nd methylation estimated with blood sample from both genders had heavier dyspigmentation. The cases with lower ability of 2nd methylation estimated with urine sample had heavier hyperkeratosis in palm and sole, and dyspigmentation. Odds ratios of prevalence of any skin lesions relating to chemical form of arsenic in blood adjusted with gender and age were the highest in monomethyl arsenic and the 2nd in dimethyl arsenic. In other words, the individual with less ability of 2nd than 1st methylation and resulted to accumulate monomethyl arsenic in their body had sever skin lesions, especially dyspigmentation. Significant improvement of skin lesions were observed in the first year after the changing drinking water to low arsenic, but the pace of improvement was slow in the ensuing years. There was no correlation between the ability of methylation and the improvement of skin lesions.
Relatively low dose (1,4 and 8 micro M) of trivalent inorganic arsenic (sodium arsenite) enhanced the proliferation of normal human epidermal keratinocytes (NHEK) via production of GM-CSF and TGF-alpha by themselves. Increase of daughter chromosome exchange ratio was also observed in the NHEK culture with existence of arsenic. The proliferation of mouse dermal fibroblast (3T3) cells was induced by low dose of arsenic. The both enhancements of proliferation in epidermal keratinocyte and dermal fibroblast induced by arsenic were suggested to be association with hyperkeratosis observed in residents who had been exposed to arsenic via drinking water for long periods.