Altered activity of heme biosynthesis pathway enzymes in individuals chronically exposed to arsenic in Mexico

Our objective was to evaluate the activities of some enzymes of the heme bi osynthesis pathway and their relationship with the profile of urinary porph yrin excretion in individuals exposed chronically to arsenic (As) via drink ing water in Region Lagunera, Mexico. We selected 17 individuals from each village studied: Benito Juarez, which has current exposure to 0.3 mg As/1; Santa Ana, where individuals have been exposed for more than 35 years to 0. 3 mg As/1, but due to changes in the water supply (in 1992) exposure was re duced to its current level (0.1 mg As/1), and Nazareno, with 0.014 mg As/1. Average arsenic concentrations in urine were 2058, 398, and 88 mu g As/g c reatinine, respectively. The more evident alterations in heme metabolism ob served in the highly exposed individuals were: (1) small but significant in creases in porphobilinogen deaminase (PBG-D) and uroporphyrinogen decarboxy lase (URO-D) activities in peripheral blood erythrocytes; (2) increases in the urinary excretion of total porphyrins, mainly due to coproporphyrin III (COPROIII) and uroporphyrin III (UROIII); and (3) increases in the COPRO/U RO and COPROIII/COPROI ratios. No significant changes were observed in urop orphyrinogen III synthetase (UROIII-S) activity. The direct relationships b etween enzyme activities and urinary porphyrins, suggest that the increased porphyrin excretion was related to PBC-D, whereas the increased URO-D acti vity would enhance coproporphyrin synthesis and excretion at the expense of uroporphyrin. None of the human studies available have reported the marked porphyric response and enzyme inhibition observed in rodents. In conclusio n, chronic As exposure alters human heme metabolism; however the severity o f the effects appears to depend on characteristics of exposure not yet full y characterized.