20:T50e,Castellino, N., and Aloj, S. (1969).Brit. J. industr. Med.,26, 139-143. Intracellular distribution of lead in the liver and kidney of the rat. The distribution of lead in intracellular fractions of liver and kidney has been studied in rats for nine days after intravenous injection of 100 μg. of lead (²¹⁰Pb) per rat. The radioactivity and the protein nitrogen have been measured in the homogenates and in the nuclei, mitochondria, microsomes, and cell sap. Lead penetrates the cells quickly, being present in all fractions one hour after injection. During the first 72 hours the relative amounts of lead in the different fractions varied, which ruled out the possibility that all the differences could be explained by redistribution after homogenization. The distribution of the metal within the cell probably depends upon differences in the nature and the stability of bonding to intracellular structures. The binding of lead within the mitochondria seemed to be particularly stable, only 24·4% of the radioactivity being removed by washing with 0·25 m sucrose or 0·001 m ethylenediaminetetra-acetate or 0·001 m diethylenetriaminopenta-acetate in 0·25 m sucrose. This finding is discussed in relation to haem biosynthesis within the mitochondrion.21:T4f4,1. Very low concentrations of Pb2+ decrease the capacity of rat heart mitochondria, oxidizing pyruvate plus malate, to remove Ca2+ from the medium. 2. The primary effect is on the rate of Ca2+ sequestration; this is reflected in the overall extent of Ca2+ removal. 3. Pb2+ has at least two separate actions. Below about 0.5 nmol/mg of protein, it acts solely by competing with Ca2+ (Ki = 0.4 muM); above this concentration it also inhibits the production or use of respiratory energy, so that at 1 nmol of Pb2+/mg of protein, Ca2+ removal is almost completely abolished. 4. Pb2+ inhibits coupled and uncoupled respiratory O2 use by mitochondria oxidizing pyruvate plus malate, but at higher concentrations than those that affect Ca2+ removal; similar concentrations of Pb2+ inhibit pyruvate uptake, but not malate uptake, by the mitochondria. 5. Mg2+ only decreases Ca2+ removal by competition, and is a far-less effective competitor than Pb2+ (Ki = 0.15 mM). It is possible that the primary cause of the second effect of Pb2+ is displacement of membrane Mg2+. 6. The consequences of these results are discussed in terms of the possible involvement of heart mitochondria in excitation-contraction coupling, and the Pb2+ levels that might occur in heart tissue in vivo.

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