pH studies of malignant tissues in human beings.

On the basis of extensive studies, it has long been contended by many investigators that the hydrogen ion concentration of malignant tissues differs from that of normal tissues in a characteristic way. The results obtained, however, are highly controversial. Many workers have found an alteration of pH to the alkaline side (1, 4, 5, 9, 14, 16). Others have found an alteration to the acid side (7, 8, 13, 15, 20). Still others (2, 11, 23) have found no specific pH change in neoplastic tissues. These wide differences in results are explained by Stern and Willheim in several ways: 1. The hydrogen ion concentration of living tissue undergoes constant variations as a result of continuous metabolic processes. 2. Comparisons with values of normal tissues are few, in experimental animal work as well as with human tumors. 3. The technic used, the changes introduced by the method itself and the individual interpretation of results all contribute to the varying conclusions drawn as to pH alteration in neoplastic tissues. Some workers have tested freshly prepared extracts of tumors by a colorimetric method while others have injected indicator substances into tumor-bearing animals. Both quinhydrone and glass electrodes have been used in tissue cultures, in material surgically-removed in vitro and in living, lightly anaesthetized animals in vivo. Many, including Voegtlin, Kahler and Fitch (22) agree that the glass electrode is best suited for the purpose of study of this problem. I t has long been demonstrated that the presence of oxidizing and reducing substances derived from tissues did not introduce any error in the pH determinations made by the bulb type of glass electrode (22). Voegtlin, DeEds, Kahler and Rosenthal (19) in 1929 demonstrated that the insertion of bulb type of electrodes into skeletal muscle would give rough estimations of pH changes under varying physiological conditions. Snell and Biffen ( 17), in discussing the advantages of the glass electrode, state that "the glass electrode is not affected by oxidation-reduction potentials in the solution. It has no salt or protein error and usually comes to equilibrium immediately. Most instruments have incorporated temperature compensators. Many types of glass electrodes are available and may frequently be used interchangeably with those in the original apparatus." Our study was carried out at the Cook County Hospital in Chicago where pH determinations were made by means of the Beckman pH meter, Model G, using both glass bulb type and capillarytype electrodes (No. 1190 and No. 1190 )K 5) on tissues freshly removed at surgery (Figs. 1 and 2). The Beckman 1190 X 5 glass electrode is built with a special pH sensitive glass bulb blown on the end of standard lead glass tubing. The bulb is subsequently shaped into a taper for ease of inserting into soft materials. The buffer solution used in the tip of the glass electrode is such that when this electrode is employed in combination with t h e standard 1170 Reference Calomel Electrode it provides the proper emf-pH characteristics to the Model G circuit so that the resulting measurements made with the instrument read directly in pH units. The solution used in the glass electrode does not deteriorate with age. In the pH range from 0 to approximately 9.5-10.0 pH, glass electrodes act quite accurately as a hydrogen electrode. The calomel electrode consists of a permanently filled, calomel-mercury internal, and an external body around it which is kept filled with saturated KCL solution. The liquid junction potentials between the solution under measurement and the KCL solution is achieved b y adjustment of the concentrations of the components of the special filling solution used in the glass electrode. Because the composition of all of the solutions used in the two electrodes is always the same and the