Arsenic Methylation, Urinary Arsenic Metabolites and Human Diseases: Current Perspective

摘要

National Taiwan University College of Medicine, Taipei, Taiwan; Division of Endocrinology and Metabolism of the Department of Internal Medicine and Department of Medical Research and Development, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan; Division of Endocrinology and Metabolism of the Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; School of Public Health, Taipei Medical University, Taipei, Taiwan; Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Taipei, Taiwan Arsenic can cause cancerous and non-cancerous human diseases. Inorganic arsenic from drinking water is the most common source of human exposure. Pentavalent arsenate can be reduced to trivalent arsenite in the blood, which is taken up mainly in the liver and metabolized by a sequence of reduction and oxidative methylation. A proportion of the inorganic arsenicals together with methylated metabolites are excreted in urine. Analyses of the urinary arsenic profile can give a hint to the methylation capacity of exposed individuals. All studies evaluating the association between urinary arsenic profiles and human diseases nowadays measure mainly the inorganic arsenate and arsenite and the two organic forms of methylated metabolites: the pentavalent form of monomethy-larsonic acid (MMA~V) and dimethylarsinic acid (DMA~V). A review of the current literature suggests that reduced methylation capacity with increased MMA~V percentage, decreased DMA~V percentage, or decreased DMA~V/MMA~V is associated with skin lesions, skin cancer, bladder cancer, peripheral vascular disease, muscle cramps and structural chromosome aberrations in peripheral lymphocytes obtained from exposed subjects. The detection of the recently identified more toxic trivalent forms of methylated metabolites in urine awaits further confirmation.