In 1938, Jacobs, et al. discussed differences in the permeability of the erythrocytes of rat and mouse to erythritol, mannitol, glycerol, and thiourea. Rat erythrocytes were more permeable to glycerol than to thiourea, whereas the reverse was true for mouse erythrocytes. Mouse erythrocytes also displayed a high degree of permeability to erythritol. However, this same substance penetrated rat cells much more slowly. Small but recognizable permeability differences were soo demonstrated among a number of species within a single genus. Levine (1943) investigated species differences in rates of osmotic hemolysis within the genus Peromyscus. The four species studied were: P. eremicus fraterculus, P. leucopus noveboracensis, P. gossypinus palmarius, and P. T. truei. Consistent differences in hemolysis times were demonstrated and it was possible to identify each species with certainty. Later experiments (LeFevre, 1948) suggested that glycerol and glucose did not enter the human red cell by simple diffusion, but rather that these penetrants were transported into the erythrocyte by an active metabolic system in which at least one essential link involved a sulfhydryl group Jacobs, et al. (1950) examined the inter-class erythrocyte permeabilities of mammals, birds, reptiles, amphibians, and fish to isosmotic solutions of urea, thiourea, glycerol, and ethylene glycol. Their results, which were generally consistent within a given class, indicated an unusually high permeability of glycerol and ethylene glycol in bird erythrocytes, and for urea in mammalian red cells. It was also found that the permeability of chicken red blood cells differed noticeably from the rather uniform pattern seen in the erythrocytes of such species as the pigeon, herring gull, English sparrow, pheasant, and turkey. In 1961, Hunter studied the effect of butanol on the permeability of human, rabbit, sheep, and chicken erythrocytes to glycerol, monoacetin, thiourea, and ammonium chloride. This work suggested that when the movement across the cell membrane depended on simple diffusion, butanol increased the permeability, but the effect of butanol on facilitated diffusion was inhibitory. A subsequent investigation by Hunter, George, and Ospina (1965) in which n-butyl alcohol and tannic acid were used, provided further help in distinguishing between simple and facilitated diffusion systems. This work suggested that a carrier system was present for glycerol in the erythrocytes of the rabbit, mouse, and man. During his study of hexose transport in beef erythrocytes, Laris (1967) noted considerable variation in the capacity of cells from different cattle to accumulate fructose both in the presence and in the absence of a metabolic inhibitor. Upon closer examination it was shown that beef erythrocytes could be divided into two distinct groups on the basis of differences in the fructose transport system. In a recent study, Hunger (1976) added six small mammals to the list of species in which a number of different nonelectrolytes penetrate the erythrocyte by facilitated diffusion. One of these six was the deer mouse (P. maniculatus), and it, like the other five species examined, was shown to have a carrier which is shared by glycerol and ethylene glycol. Hunger also obtained data which hinted at the possibility of permeability differences among separate populations of deer mice (Hunter, personal communication). Such findings prompted the present study of the permeability of red cells to glycerol in two different populations of the pinyon mouse (P. truei). In addition to this population comparison, the glycerol permeabilities of two closely related species, P. truei and P. californicus, were investigated

Early studies of the permeability of the animal cell membrane were difficult to compare, because of the variety of cell types involved. In the late nineteenth century, workers chose to use erythrocytes due to their advantages over using a variety of cell types. With erythrocytes a comparison could be developed between strictly homologous cells of many different species. Erythrocytes are easily obtainable and mature cells are separate from all other cells of the body as well as from each other. Of even greater importance is the fact that the mature erythrocyte’s major function is the uptake of the greatest possible amount of gases and solutes in the shortest possible time and elimination of these materials without loss or change. The erythrocyte eliminates the complications arising from metabolism of the penetrant being studied. This is attributed to the fact that the erythrocyte is metabolically almost inactive. TO illustrate this point, the human erythrocyte has a rate of glucose utilization of 0.019 ug/hr/million cells while the human leucocyte’s glucose utilization rate is 7.24 ug/hr/million cells or nearly 380 times as great (Guest et al., 1953). The importance of a nearly inactive cell is the lack of complications due to interpretation of data as a function of metabolic processes rather than membrane transport.

A Thesis Submitted to the Faculty of Medicine, in Fulfilment of the Requirements for the Degree of • Doctor of Philosophy in the Department of Chemical Pathology, School of Pathology and the South African Institute for Medical Research, University of the Witwatersrand Medical School, Johannesburg, South Africa. December 1991. / Numerous studies have assessed the effects of single fatty acids on various aspects of lipid metabolism, particularly cancer. Established cell lines have largely been used for this purpose. The choice of control cells, however, has often been inappropriate. There is also a surprising lack of knowledge of the effects of fatty acids in the 'real world", in which normal cells in vivo are presented with mixtures of dietary fatty acids. Before transformed cells can be used as models of disease states, it is essential to fully understand fatty acid metabolism in normal (control) cells / IT2018

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