The effect of low lead doses in vitro and in vivo on the d-ala-d activity of erythrocytes, bone marrow cells, liver and brain of the mouse.
The d-ala-d activity in erythrocytes (RBC), femur bone marrow, liver and brain of mice was determined using a modification of the method of Berlin and Schaller (1974). In vitro incubation of lead acetate (PbAc) with these tissues resulted in a dose-dependent inhibition of the d-ala-d activity. The lead concentration which caused a 50% inhibition of the d-ala-d activity after 10 min incubation [ED-50(10 min)] was 0.78 mg PbAc/femur bone marrow, 3.72 micrograms PbAc/ml RBC, 15.85 micrograms PbAc/g brain and 43.05 micrograms PbAc/g liver. An increase in the incubation time to 60 min reduced these ED-50 values between 44% for the erythrocytic enzyme and 67% for the brain enzyme. In vivo treatment of mice with oral lead administration (absorbed dose range: 1-100 micrograms PbAc/kg b.w.) for 1 or 3 months led to a dose-dependent and organ-specific inhibition of the d-ala-d activity. After 3 months of oral lead supply the maximum enzyme inhibition (54%) was found in the bone marrow. At the same time the lowest enzyme inhibition could be seen in the brain which retained 73% of its activity. The erythrocytic and liver enzyme activity was 71% and 72% resp. of the appropriate control. Within 3 weeks after completing the oral lead administration the brain enzyme activity was completely restored. The erythrocytic and liver enzyme activities were still significantly, but not very markedly inhibited, whereas the bone marrow d-ala-d remained seriously depressed. According to these experiments, the lead dose which causes a long term inhibition of the bone marrow and erythrocytic d-ala-d activities is assumed to range between 50 and 100 micrograms PbAc/kg b.w. and day, as an absorbed dose.
D000818:Animals; D001853:Bone Marrow / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000201:enzymology*; D007854:Lead / Q000633:toxicity*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D009928:Organ Specificity; D009942:Organometallic Compounds; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors* / Q000097:blood; D013997:Time Factors
D009942:Organometallic Compounds; D007854:Lead; D000623:Porphobilinogen Synthase; C008261:lead acetate