Cytochrome P-450 system dependent depression of delta-aminolevulinic acid dehydratase activity by bromobenzene in...

Male Wistar rats (200-230 g) were treated with bromobenzene in soybean oil intraperitoneally (i.p.) (4 mmol/kg) once a day for 1 or 2 days while control rats received soybean oil alone. delta-Aminolevulinic acid dehydratase (ALA-D) activity was depressed to 80% and 43% in bone marrow after 24 h and 48 h, respectively. ALA-D activity was also depressed significantly in the liver after the administration of bromobenzene while the activity in peripheral erythrocytes was not altered. After the administration of bromobenzene, the concentration of reduced non-protein sulfhydryls in liver was the lowest at 24 h and increased thereafter. No significant change was observed in the activity of delta-aminolevulinate synthase in liver. The decrease of ALA-D activity was also reproducible in vitro. The 105 000 g supernatant fractions of rat bone marrow lyzates as ALA-D source were incubated with liver microsomes prepared from rats treated with phenobarbital. ALA-D activity was decreased by bromobenzene but no decrease was observed when the microsomes were preincubated with CO to inhibit cytochrome P-450. The effect of bromobenzene on ALA-D purified from rat erythroid cells was studied in incubations containing a reconstituted cytochrome P-450 system prepared from rat liver. The decrease of ALA-D activity was proportional to both the incubation time and to the concentration of P-450 while no decrease was detected when P-450 was inhibited by CO before the incubation.