Arsenic methylation capacity

Drobna, Z., Xing, W., Thomas, D.J. and Styblo, M. (2006) shRNA silencing of AS3MT expression minimizes arsenic methylation capacity of HepG2 cells. Chemical Research in Toxicology, 19(7), 894-98. 

Chiou HY, Hsueh YM, Hsieh LL, Hsu LI, Hsu YH, Hsieh FI, Wei M-L, Chen HC, Yang HT, Leu LC, Chu TH, Chen-Wu C, Yang MH and Chen CJ (1997) Arsenic methylation capacity, body retention, and null genotypes of glutathione S-transferase Ml and T1 among current arsenic-exposed residents in Taiwan. Mutat Res 386 197-207. 

Chen, Y, Wu, E, Liu, M., Parvez, E, Slavkovich, V, Eunus, M., Ahmed, A., Argos, M., Islam, T., Rakibuz-Zaman, M., Hasan, R., Sarwar, G., Levy, D., Graziano, 1. Ahsan, H. (2013) A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh. Environmental Health Perspectives, 121, 832-838. 

This research is an outgrowth of an earlier project which sought to characterize the mechanism of arsenic metabolism in a population currently drinking arsenic-contaminated water in Taiwan. There were three parts to the study, a cohort study, a case control study for skin cancer, and a study of intra-individual variability associated with chronic arsenic exposure. The latter three research projects are complete and being submitted for publication. The results of this research are highly relevant since they indicate that alterations in methylation capacity may affect arsenic carcinogenesis. 

The relative concentrations of the arsenic methylation metabolites in human urine have been used as a surrogate to compare methylation capacity between individuals and between populations (90). For example, a much lower portion (2.2%) of urinary MMA(V) was found in native Andean women (86), compared with 10-20% urinary MMA(V) in other populations. In another study of northern Argentina population, children were found to have a significantly higher percentage of inorganic arsenic (50%) in their urine samples than the adult women (32%) (91). 

The one exception is the capacity of some micro-organisms to methylate certain metals, e.g. arsenic, antimony and mercury, probably as a kind of detoxification mechanism. Methylcobal-amin is the only organometallic compound known to have a physiological function in life processes. 

The intermediate of the irreversible isomerization can be isolated. The EMc2 unit is <7 bonded in the educt it is a centre of basic activity, shoeing tendency for reactions with electrophiles. Thus the electron-rich state of the atoms of group 15 elements leads to irreversible isomerization with shifting of one methyl group from the PR3 ligand to arsenic or antimony, respectively. The donor capacity of the transition metal is enlarging this ability. 

E. Redistribution of metals to the brain. Despite its capacity to increase survival in acutely poisoned animals, BAL has been associated with redistribution of mercury and arsenic into the brain. Avoid use in chronic elemental mercury poisoning or alkyl (eg, methyl) mercury poisoning, where the brain is a key target organ. 

Inorganic arsenic, MMA, and DMA were found to be the only metabolic forms of As in urine of volunteers who ingested 125, 250, 500, or 1000//g sodium As daily for 5 days (Buchet et al. 1981a). The amounts of iAs, MMA, and DMA excreted in urine on day 5 (taken separately or together) correlated significantly with daily ingested dose. As noted above, this study provided equivocal evidence that the capacity for methylation of As could be saturated at high levels of iAs intake. 

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