Interindividual variability in the urinary excretion of inorganic arsenic metabolites by C57 BL/6J mice: possible involvement of a thiol/disulfide exchange mechanism.
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 micrograms/24 h, variability (cv) of 33%), SAM (7.5-67.2 micrograms/24 h, cv of 38%), urea (9.5-89.7 mg/24 h, cv of 36%), ASi (0.1-1.6 microgram/24 h, cv of 48%), MMA (0.17-2.1 micrograms/24 h, cv of 50%), DMA (0.73-8.13 micrograms/24 h, cv of 32%) and total arsenic metabolites (1.0-10.4 micrograms/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.
Morel
G
G
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
Cluet
J L
JL
Telolahy
P
P
Yang
H M
HM
Thieffry
N
N
de Ceaurriz
J
J
D000818:Animals; D001152:Arsenicals / Q000652:urine*; D018053:Arsenites / Q000378:metabolism*; D003404:Creatinine / Q000652:urine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017670:Sodium Compounds / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D013723:Teratogens / Q000378:metabolism; D014508:Urea / Q000652:urine
D001152:Arsenicals; D018053:Arsenites; D017670:Sodium Compounds; D013723:Teratogens; C017947:sodium arsenite; D014508:Urea; D003404:Creatinine; C020300:monomethylarsonic acid