VOL. 12 (1953) 



EFFECTS OF INSULIN ON MELANOMA 



331 



TABLE I 



COMPARATIVE METABOLIC ACTIVITIES OF NORMAL MOUSE BRAIN AND S-9I MELANOMA SLICES IN HANK- 

 SIMMS MEDIUM PLUS 0.03 M KHCO3 AND 0.625% DEXTROSE. THE RESULTS OF SINGLE EXPERIMENTS 

 UNDER THE SAME CONDITIONS WITH EMBRYONIC MOUSE BRAIN {cU. I WEEK OLD) AND TOTAL EMBRYO 



(less THAN I WEEK OLD) ARE SHOWN FOR COMPARISON 



3 All Q values expressed as /il/mg dry wt/hr. (Calculation based on 23% dry wt except melanoma 

 calculations based on 20% dry wt). 



b Became +5.1 in presence of o.i mg/ml Neotetrazolium where Qq^ was — 1.3 and R.Q. — 1.2. 



similar manner under the same experimental conditions {Qq^ = 7.2, (^co = 4-7> and 

 Q^^ = 3.0). Lactic acid determinations, which were made essentially by the method of 

 Barker-Summerson^, showed that with melanoma slices in Hank-Simms medium with 

 0.625 °o dextrose virtually all of the manometrically indicated acid could be accounted 

 for as lactic. Thus in four experiments the average (^co, was 7.3 (range 4.5 to 8.8), and 

 the average <?i^ctic was 7.3 (range 5.3 to 10. 0). In the presence of oxygen the average 

 Q2^ was 4.3 (range 3.7 to 5.0) and the average Qf^lii^ was 4.3 (range 4.1 to 4.7). Similarly 

 in brain the Qq^ in two experiments was 2.7 and 2.1 the respective lactic values, 2.1 

 and 2.1. In the second of these experiments (^co, was 5.7, and the Q^^l^^ 4-0- All subsequent 

 experiments were based upon measurements of COg evolution only, and pH measure- 

 ments were frequently made to provide a general check on the manometric data. 



Action of phenol, magnesium, and insulin on brain slices 



The ^c§ of brain could be raised to the melanoma level by the combined effects of 

 increasing the magnesium level from o.oi mg to 0.4 mg per ml plus the addition of 0.25 

 ml of commercial insulin per ml of Hank-Simms medium to give a final concentration 

 per ml of 4 units crystalline zinc-insulin and 0.4 mg phenol (the phenol present in 

 commercial insulin as a preservative) . Further experiments showed that this action of 

 commercial zinc-insulin preparations, which was largely additive to the magnesium 

 effect (Fig. i), could be duplicated by the use of equivalent concentrations of phenol 

 without added insulin. Furthermore, the crystalline, preservative-free zinc-insulin was 

 without significant effect (Fig. 2). Both the usual zinc-insulin crystals, as well as 

 the preparation free from hyperglycemic factor, gave negative results. The same 

 negative results were also obtained when low-zinc insulin was used. However, without 

 a single exception (over 20 experiments) addition of phenol (with or without insulin), 

 and/or raising the magnesium level, increased the Qq^ of brain although the magnitude 

 of the stimulation varied in different preparations. Thus in 4 typical experiments 



References p. 346. 

 21 



