Altered urinary porphyrin excretion in a human population chronically exposed to arsenic in Mexico.
1. A detailed study of the urinary excretion pattern of porphyrins in humans chronically exposed to As via drinking water was performed using high performance liquid chromatography (HPLC) 2. Thirty-six individuals (15 men and 21 women) were selected from a town which had 0.400 mg L-1 of As in drinking water. The control group consisted of thirty-one individuals (13 men and 18 women) whose As concentration in drinking water was 0.020 mg L-1. 3. The major abnormalities in the urinary porphyrin excretion pattern observed in arsenic-exposed individuals were: (a) significant reductions in coproporphyrin III excretion resulting in decreases in the COPRO III/COPRO I ratio, and (b) significant increases in uroporphyrin excretion. Both alterations were responsible for the decrease in the COPRO/URO ratio. 4. No porphyrinogenic response was found in individuals with urinary As concentrations below 1,000 micrograms of As g-1 of creatinine. However, as arsenic concentrations exceeded this value, the excretion of porphyrins (except coproporphyrin III) increased proportionally. 5. The prevalence of clinical signs of arsenicism showed a direct relationship to both As concentration in urine and time-weighted exposure to As. A direct relationship between time-weighted exposure and alterations in urinary porphyrin excretion ratios was also observed. 6. The alterations found are compatible with a lower uroporphyrinogen decarboxylase activity in arsenic-exposed individuals. However, the similarities in the urinary porphyrin excretion pattern between As-exposed individuals and Dubin-Johnson syndrome patients suggest that impairments in the excretion of coproporphyrin isomers may also contribute to the pattern observed.
García-Vargas
G G
GG
MRC Toxicology Unit, University of Leicester, UK.
Del Razo
L M
LM
Cebrián
M E
ME
Albores
A
A
Ostrosky-Wegman
P
P
Montero
R
R
Gonsebatt
M E
ME
Lim
C K
CK
De Matteis
F
F
D000328:Adult; D000368:Aged; D001151:Arsenic / Q000652:urine; D020261:Arsenic Poisoning; D002851:Chromatography, High Pressure Liquid; D003306:Coproporphyrins / Q000652:urine*; D003404:Creatinine / Q000652:urine; D004326:Drinking; D005260:Female; D006801:Humans; D007566:Jaundice, Chronic Idiopathic / Q000378:metabolism; D008297:Male; D008800:Mexico; D008875:Middle Aged; D012044:Regression Analysis; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism; D014578:Uroporphyrins / Q000652:urine*; D014874:Water Pollutants, Chemical / Q000506:poisoning* / Q000652:urine
D003306:Coproporphyrins; D014578:Uroporphyrins; D014874:Water Pollutants, Chemical; C026971:coproporphyrin III; C031467:coproporphyrin I; D003404:Creatinine; D014575:Uroporphyrinogen Decarboxylase; D001151:Arsenic