Abstract
The 24-h urine of 75 C57 BL/6J mice injected s.c. with 0.5 mg/kg arsenic as sodium arsenite were examined for creatinine, S-adenosylmethionine (SAM), urea and inorganic arsenic metabolites including inorganic arsenic (ASi), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). There was interindividual variability of about a 10-fold range in the 24-h urinary excretion of creatinine (80–642 μg/24 h, variability (cv) of 33%), SAM (7.5–67.2 μg/24 h, cv of 38%), urea (9.5–89.7 mg/24 h, cv of 36%), ASi (0.1–1.6 μg/24 h, cv of 48%), MMA (0.17–2.1 μg/24 h, cv of 50%), DMA (0.73–8.13 μg/24 h, cv of 32%) and total arsenic metabolites (1.0–10.4 μg/24 h, cv of 31%). Interindividual differences, varying by as much as 5–7-fold, were also found in the urinary proportion of ASi (3–23%, cv of 41%) and MMA (5–22%, cv of 37%), but not in the urinary proportion of DMA (64–90%, cv of 7%). The 24-h urinary excretion of all arsenic metabolites correlated with the 24-h urinary excretion of urea ( r = 0.81), creatinine ( r = 0.88) and SAM ( r = 0.83) as did the 24-h urinary excretion of urea with creatinine ( r = 0.94) and SAM ( r = 0.86), and the 24-h urinary excretion of creatinine with SAM ( r = 0.94). Taken together, these results suggest that the overall intracellular glutathione (GSH)-dependent redox state, as reflected by the 24-h urinary excretion of SAM and creatinine, is involved in the interindividual variability in total arsenic metabolite excretion by C57 BL/6J mice. These preliminary results were also discussed with regard to the involvement of intracellular GSH-dependent redox state in the regulation of the reduction and of the methylation steps of arsenic, and to interindividual variability in the urinary excretion of total arsenic metabolites as a possible complicating factor in the biological monitoring of occupational exposure to arsenic.
Published Version
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