Monomethylarsonous Acid (MMAIII) Is More Toxic Than Arsenite in Chang Human Hepatocytes

• Published in: Toxicology and applied pharmacology 2000-03, Vol.163 (2), p.203-207
• Main Authors: Petrick, Jay S., Ayala-Fierro, Felix, Cullen, William R., Carter, Dean E., Vasken Aposhian, H.
• Format: Article
• Language: English
• Subjects: arsenate; Arsenates - toxicity; Arsenic - chemistry; arsenite; Arsenites - toxicity; Biological and medical sciences; Cacodylic Acid - chemistry; Cacodylic Acid - toxicity; Cell Survival - drug effects; Cells, Cultured; Chang human hepatocytes; Chemical and industrial products toxicology. Toxic occupational diseases; Culture Media; dimethylarsinic acid; DMA; DMAV; DMPS; Humans; L-Lactate Dehydrogenase - analysis; LDH; Liver - drug effects; Medical sciences; Metals and various inorganic compounds; MMAIII; MMAV; monomethylarsonic acid; monomethylarsonous acid; Organometallic Compounds - toxicity; potassium; Potassium - analysis; Toxicology; XTT
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1999.8872

Methylation has been considered to be the primary detoxication pathway of inorganic arsenic. Inorganic arsenic is methylated by many, but not all animal species, to monomethylarsonic acid (MMAV), monomethylarsonous acid (MMAIII), and dimethylarsinic acid (DMAV). The AsV derivatives have been assumed to produce low toxicity, but the relative toxicity of MMAIII remains unknown. In vitro toxicities of arsenate, arsenite, MMAV, MMAIII, and DMAV were determined in Chang human hepatocytes. Leakage of lactate dehydrogenase (LDH) and intracellular potassium (K+) and mitochondrial metabolism of the tetrazolium salt XTT were used to assess cytotoxicity due to arsenic exposure. The mean LC50 based on LDH assays in phosphate media was 6 μM for MMAIII and 68 μM for arsenite. Using the assay for K+ leakage in phosphate media, the mean LC50 was 6.3 μM for MMAIII and 19.8 μM for arsenite. The mean LC50 based on the XTT assay in phosphate media was 13.6 μM for MMAIII and 164 μM for arsenite. The results of the three cytotoxicity assays (LDH, K+, and XTT) reveal the following order of toxicity in Chang human hepatocytes: MMAIII > arsenite > arsenate > MMAV = DMAV. Data demonstrate that MMAIII, an intermediate in inorganic arsenic methylation, is highly toxic and again raises the question as to whether methylation of inorganic arsenic is a detoxication process.