HEAVY METALS 469 



This approach has the advantage that we need not postulate that ions 

 are able to penetrate the cell rapidly; although, as just mentioned, there 

 is some evidence for rapid passage of metals through the membrane, it 

 is generally true, considering all the organisms studied, that cations, 

 especially di- and trivalent cations, do not move easily into cells by dif- 

 fusion (84). The concept that the initial uptake is an adsorption, or 

 ion exchange, process has the additional advantage of explaining both 

 ion competition effects and the fact that uptake of copper is accom- 

 panied by roughly equal extrusion of other ions. Nor does a surface 

 adsorption require that the cell be living or even metabolizing nor- 

 mally; it has been noted (291) that uptake of several materials con- 

 tinues long after enough toxicant has been absorbed completely to 

 prevent spore germination. 



Against an adsorption hypothesis, it may be urged that the uptake 

 of some materials is so large that the classical monomolecular film 

 could not accommodate the observed toxicant (290). 



To test these two hypotheses, the most direct approach is provided by 

 model experiments on the uptake of methylene blue by bacteria (238, 

 239) and by ascospores of Neurospora tetrasperma (407). The uptake 

 reaction is independent of temperature; a metabolically powered ac- 

 cumulation would have a high temperature coefficient. Dead cells 

 adsorb dye as rapidly and completely as living cells. Different cations 

 compete with each other for a limited number of sites; as in yeast (356, 

 357), it appears that the cell surface has a countable number of more 

 or less strongly negative binding sites. Exploration of the uptake-con- 

 centration relation does not appear so profitable; any type of accumula- 

 tion would show saturation effects as the external concentration is 

 raised. 



If it proves possible to regard the initial rapid uptake of metals as 

 a surface adsorption, then the toxic action of heavy metals can be visu- 

 alized, as already mentioned, as composed of a rapid stage of uptake at 

 the surface followed by a slower penetration, perhaps through a dam- 

 aged membrane, into the interior of the cell. Alternatively, the metal 

 may enter as a coordination complex. 



Effects of sorbed metals upon the cell surface must be considered as 

 a possibility, although it seems doubtful that the major site of toxic 

 action is outside the permeability barrier. Copper reduces the perme- 

 ability of the erythrocyte to glycerol (84), and heavy metals, especially 

 mercury, depress phosphate uptake by bacteria (294). Silver increases 

 the loss of phosphorus from fungus spores, although mercury does not 

 (288). Interference with catabolic, anabolic, or carrier mechanisms out- 

 side of or on the plasma membrane is also a possibility, as in the action 



