Toxicity of Sulphonamide Drugs to Cells in Vitro
| Autor: | E. N. Willmer, F. Jacoby, P. B. Medawar |
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| Rok vydání: | 1941 |
| Předmět: | |
| Zdroj: | BMJ. 2:149-153 |
| ISSN: | 1468-5833 0959-8138 |
| DOI: | 10.1136/bmj.2.4204.149 |
| Popis: | The administration of sulphonamide drugs by injection or by mouth for the prevention and treatment of wound infec tion is in many cases giving place to a more direct method, in which the powdered drugs are applied locally to the wound surfaces (Jensen, Johnsrud, and Nelson, 1939; Legroux, 1940; Colebrook, 1940; Hawking and Piercy, 1941 ; Cole brook and Francis, 1941; and others). The first method yields concentrations in the blood and tissue fluids usually ranging from 1: 10,000 to 1:100,000, while the second establishes local concentrations ranging from saturation strength down wards. This second method raises problems concerning the toxicity of sulphonamide drugs to living cells which could hardly be expected to arise in acute form after other methods of treatment. Tissue culture provides one method of studying problems of this sort, because it is capable to some extent of reproducing in vitro the influence of the drugs on the behaviour of the various types of cells which play a part in wound healing. By means of it one should be able not only to rank a series of drugs in the order of their toxicity to living cells, but also to obtain a clear idea of the order of magnitude of the concentrations which are lethal to them. The drugs chosen for investigation were sulphanilamide, sulphathiazole, sulphapyridine, and (in some tests) sulpha diazine; and various aspects of their influence on the behaviour in vitro of cells of three main types-fibroblasts, macrophages, and epithelia-have been put on record. In each case it has been possible to draw an instructive com parison between the action of the sulphonamide drugs and that of proflavine. The method of direct application has been kept con stantly in mind. For instance, a comparison of the drugs at equal or chemically equivalent concentrations alone would be misleading, for their effective toxicity depends largely upon solubility, and on other factors-such as the rate of transport from a site of local application-which them selves largely depend upon solubility. The basic cultiva tion media-adult chicken plasma or serum, in some cases with the addition of chick embryonic extract-are those which have come to be regarded as standard in cultivation work. None of the sulphonamide drugs affects the coagu lation of plasma, and none is notably surface-active. Except with the highest concentrations of sulphanilamide, where a slight but significant osmotic effect must be exerted, the interpretation of experimental results is not therefore complicated by secondary reactions of the reagents employed. Sulphonamide drugs prove, however, to be considerably more soluble in serum than in Tyrode's solution (see table, p. 153). |
| Databáze: | OpenAIRE |
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