Studies on δ-Aminolevulinic Acid Synthetase Activity in Bone Marrow in Experimental Lead Poisoned Rats

Abstract

Urinary increase of δ-aminolevulinic acid and coproporphyrin as well as basophilic stippled cells in the peripheral blood are the characteristic signs of lead poisoning. The biochemical lesion of porphyrin biosynthesis in lead poisoning is the partial inhibition of δ-aminolevulinic acid dehydratase, but whether or not δ-aminolevulinic acid synthetase is induced (stimulated) or not by lead is still unknown. This paper reports that δ-aminolevulinic synthetase activity in bone marrow in lead poisoned rats was 6.8 times higher than that of normal rats. Activity was found to increase within three or four days after lead administration and in parallel with the urinary increase of δ-aminolevulinic acid.The levels of urinary δ-aminolevulinic acid and coproporphyrin in lead poisoned rats decreased markedly following the administration of mitomycin c. This phenomenon were also observed in the case of hepatic porphyria caused by diethyl-1, 4-dihydro-2, 4, 6-trimethylpyridine-3, 5-dicarboxylate poisoned rats when treated with mitomycin c.These results strongly suggest that δ-aminolevulinic acid synthetase activity is induced either directly or indirectly by lead. Excessive δ-aminolevulinic acid thus formed seems to overcome the partial blocking of δ-aminolevulinic acid dehydratase resulting in the increased formation of coproporphyrin in lead poisoning.