Effects of Sucrose and Dextran on the Toxicity of Lead to Mitochondria in the Presence of Inorganic Phosphate in vitro

The release of inorganic lead from numerous sources has recently prompted concern over its biological effects. Despite the undoubtedly harmful effects of PbZ+ on plants and animals (see e.g., Vallee & Ulmer, 1972) and the ubiquitous nature of Pi in living organisms, many workers have stressed that the effects of Pb2+ in vitro are eliminated by the presence of Pi (see, e.g., Koeppe & Miller, 1970; Scott et al., 1971 ; Bittell et al., 1974), and as a result no studies have been made of its action on oxidative phosphorylation. Mitochondria bind and accumulate Pbz+ in vitro (see, e.g., Scott et al., 1971), and there is evidence that lead ingestion by rats leads to mitochondrial damage in vivo (see e.g., Krall etal., 1971). Wehaverecentlyfound that the presence ofATPconsiderablyincreases the damage that PbZ+ does to heart mitochondria in vitro in the presence of Pi, because of the formation of a P b A T P complex that renders more of the metal soluble (D. R. Parr & E. J. Harris, unpublished work). This has prompted us to look for other factors that might influence the solubility of PbZ+ and thus help to explain the toxicity of this cation. In the present paper we show that in a KCI medium both sucrose and dextran increase the damaging effect of lead on mitochondrial phosphorylation, a process for which added Pi is essential. Rat heart mitochondria were prepared as described by Parr et af . (1975), care being taken to remove the ‘fluffy layer’ that often covers the mitochondrial pellet. The final mitochondrial suspension was supplemented with 0.5 mg of purified bovine serum