ACUTE EFFECT OF ORALLY-ADMINISTERED GALLIUM-ARSENIDE, GALLIUM NITRATEAND DISODIUM ARSENATE ON HEME-SYNTHESIS IN MALE AND FEMALE MICE

Gallium arsenide (GaAs), gallium nitrate and disodium arsenate were ea ch administered orally to mice of both sexes (Jcl:ICR strain) at varyi ng dosage levels and examined for their effects on the heme biosynthet ic enzyme system in the spleen, liver, kidney and peripheral blood. Th e results indicate that the areas most affected by administration of g allium nitrate or disodium arsenate were enzymes in the hematogenous c ells of mouse spleen, In mice of the disodium arsenate-treated groups delta-aminolevulinic acid synthase (ALAS, EC 2.3.1.37), the first enzy me in the heme biosynthetic pathway and the rate-limiting enzyme for h eme synthesis, delta-aminolevulinic acid dehydratase (ALAD, EC 4.2.1.2 4) 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 t he spleen was also observed in the gallium nitrate-treated groups, The effects of these treatments were more conspicuous in female than in m ale mice, An in vitro experiment demonstrated that activities of purif ied ALAS, ALAD and PBGD were not inhibited to any noticeable extent by arsenic compounds. These results suggest that disodium arsenate may s trongly inhibit heme biosynthesis in mouse spleen.