340 M. WOODS, K. WIGHT, J. HUNTER, D. BURK VOL. 12 (1953) 



TABLE IV 



RESPONSE OF S-9I MELANOMA SLICES TO ZINC, -± INSULIN, IN FOUR EXPERIMENTS, EACH INVOLVING 

 A DIFFERENT INDIVIDUAL TUMOR. THE VALUES REPRESENT PERCENTAGE STIMULATIONS OR INHIBITIONS 

 RELATIVE TO THE CONTROLS (WITHOUT ADDED INSULIN OR ZINC). CONTROL g^^ VALUES WERE 12. IN A, 

 12.6 IN B, 15.2 IN C, AND ID. 6 IN D. I.I y OF ZINC ION ARE APPROXIMATELY EQUIVALENT TO THE ZINC 

 PRESENT IN 4 UNITS OF CRYSTALLINE ZINC-INSULIN (ZINC CA. 0.7%). THE LOW-ZINC INSULIN HAD A 

 ZINC CONTENT OF CA. 0.017%. EXPERIMENTS A, B AND C IN HANK-SIMMS AND D IN KREBS-RINGER- 

 BICARBONATE. DEXTROSE 0.625%, O.O3 M KHCO3, 95% Ng AND 5% CO2. 



the inhibitory action of zinc. However, it should be noted that in the other response 

 pattern (Table IV, A and B) zinc alone, at 8.0 y per ml, did not inhibit acid production 

 although it did markedly counteract the stimulatory effect of insulin when the two 

 were given simultaneously. 



It is of interest that in zinc-inhibited tumors in the absence of added insulin the 

 inhibition was as great with ca. i y of zinc per ml as with 4 to 8 y of zinc. Thus in three 

 experiments the average inhibition with ca. i y zinc per ml was 28% (range 15 to 41%) 

 and with 4 to 8 y, 21 % (range 15 to 31 %)• On the other hand in three experiments where 

 ca. I y of zinc per ml did not significantly change the (2c6„ ( — 1% in all 3 experiments), 

 likewise 8 y of zinc did not cause a significant change (average — 2%, range — 9 to 5%). 

 The data show that in those tumors where zinc {in the absence of added insulin) is 

 inhibitory, a concentration of only i y zinc per ml is already saturating. 



Some tumors were found to have patterns of response to zinc and insulin inter- 

 mediate between those illustrated in Table IV. While many questions are left un- 

 answered, the data obtained indicate that zinc plays an important role in insulin 

 function (in so far as this can be determined from in vitro stimulation of anaerobic acid 

 production), and that the relative concentrations of the two substances are highly 

 critical. While Hallas-M0LLER et al.^^ have reported that addition of phosphate 

 completely neutralizes the protracted effect {in vivo response) of an insulin crystal 

 suspension containing zinc, phosphate-zinc interaction can hardly be playing a major 

 role in the present experiments. In the first place, the wide range of response patterns to 

 zinc occurred in the presence of a uniform and low level of phosphate [ca. o.ooi .17). 

 Secondly, in other experiments with S-91 melanoma, raising the phosphate level from 

 o.ooi M to 0.005 M had no effect on either (^eo, "i" on the percentage stimulation by 

 insulin. 



References p. 346. 



