Alterations in the heme biosynthetic pathway from the III-V semiconductor metal, indium arsenide (InAs).
The effects of indium and arsenic on the heme biosynthetic pathway have been well documented but the effects of indium arsenide (InAs), the next possible generation of the III-V semiconductors, are unknown. Male Syrian golden hamsters were given s.c. injections of sodium arsenite (As3+), indium chloride (In3+) or indium arsenide (InAs). Erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity was inhibited in all exposure groups, while hepatic ALAD activity was not significantly changed. In contrast, the activity of renal ALAD was found to be statistically decreased by As3+ at 10 days, but increased at 30 days, while In3+ and InAs inhibited this enzyme activity at all time points. In vitro studies showed that hepatic ALAD activity was more sensitive to In3+ than As3+, suggesting that the effects of InAs in vivo on this enzyme are due primarily to the In rather than the As moiety. Studies of urinary porphyrin excretion patterns in animals treated with InAs showed marked, early 2-4-fold increase in the excretion of the penta-, hexa- and heptacarboxyl porphyrin at 1-5 days which continued through day 30 of the study. In contrast, there was a slow and steady rise in the excretion of coproporphyrin I and III which reached a maximum at day 30. The results of these studies indicate that both the In and As moieties of InAs are biologically active following InAs exposure and that the enzymes in the heme pathway, such as ALAD, may have great utility as markers of exposure/toxicity for these agents.
Conner
E A
EA
University Program in Toxicology, University of Maryland, Baltimore 21227, USA.
Yamauchi
H
H
Fowler
B A
BA
D000622:Aminolevulinic Acid / Q000652:urine; D000818:Animals; D001151:Arsenic / Q000494:pharmacology; D001152:Arsenicals / Q000494:pharmacology*; D006224:Cricetinae; D004912:Erythrocytes / Q000201:enzymology; D006418:Heme / Q000096:biosynthesis*; D007204:Indium / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D000623:Porphobilinogen Synthase / Q000378:metabolism; D011166:Porphyrins / Q000652:urine; D013997:Time Factors
D001152:Arsenicals; D011166:Porphyrins; D007204:Indium; D006418:Heme; D000622:Aminolevulinic Acid; D000623:Porphobilinogen Synthase; C076773:indium arsenide; D001151:Arsenic