Acute Effect of Orally Administered Gallium Arsenide, Gallium Nitrate and Disodium Arsenate on Heme Synthesis in Male and Female Mice

Abstract

Gallium arsenide (GaAs), gallium nitrate and disodium arsenate were each administered orally to mice of both sexes (Jcl:ICR strain) at varying dosage levels and examined for their effects on the heme biosynthetic enzyme system in the spleen, liver, kidney and peripheral blood. The results indicate that the areas most affected by administration of gallium nitrate or disodium arsenate were enzymes in the hematogenous cells of mouse spleen. In mice of the disodium arsenate‐treated groups δ‐aminolevulinic acid synthase (ALAS, EC 2.3.1.37), the first enzyme in the heme biosynthetic pathway and the rate‐limiting enzyme for heme synthesis, δ‐aminolevulinic acid dehydratase (ALAD, EC 4.2.1.24) and porphobilinogen deaminase (PBGD, EC 4.3.1.8) activities in the spleen were markedly depressed in a dose‐dependent fashion. A similar, but apparently less marked, reduction in these enzyme activities in the spleen was also observed in the gallium nitrate‐treated groups. The effects of these treatments were more conspicuous in female than in male mice. An in vitro experiment demonstrated that activities of purified ALAS, ALAD and PBGD were not inhibited to any noticeable extent by arsenic compounds. These results suggest that disodium arsenate may strongly inhibit heme biosynthesis in mouse spleen.