VOL. 12 (1953) 



EFFECTS OF INSULIN ON MELANOMA 



337 



of two S-91 tumors from mice maintained at 40° C for 255 hours had (^co^ values of only 

 4.10 and 4.86 in the absence of additions, and only 3.08 and 4.4 respectively in the 

 presence of 4 units of low-zinc insulin plus i.i y inorganic zinc per ml. It is not known 

 whether these tumors were zinc-inhibited [cf. 

 later section and Table IV, columns 3 and 

 4) or not, but two "room temperature" tumors 

 from the same transplant generation, and 

 run simultaneously, showed Q^q^ values of 

 10.21 and 13.72 without insulin and 14.03 

 and 14.41 (respectively) with low-zinc insulin 

 plus zinc. Very prolonged exposure to high 

 temperature at least results in a marked 

 lowering of tumor Q^^ , and is associa- 

 ted with pronounced suppression of tumor 

 growth (Fig. 5). Melanoma-bearing mice held 

 at 35° C for varying periods of time, and com- 

 pared with mice held at a uniform tempera- 

 ture of 20° C, also showed much larger 

 insulin-induced stimulations of (2c6, than did 

 the low temperature series (Table II). Here, 

 too, the average control Q^^^ is lowest in the 

 high temperature series, and following the 

 addition of insulin, rises to that of the low 

 temperature series. Again prolonged exposure 

 of the tumors to high temperature (35° C) 

 was associated with a further depression of 

 both (2c6 and growth. Thus in two tumors 

 held for 44 days at 35 ° C there was a marked 

 suppression of growth (Table III), and the 

 (2c6 values were low. In one of these tumors 

 the (2c6, was 6.83, and addition of i unit 

 crystalline zinc-insulin per ml raised this value 

 only 12%. The other tumor, which was the more fibrous of the two, had a Q^q^ of only 

 3.06. In the latter case insulin increased the rate of acid production 80% [Q^q = 5-5o)- 



2.0 



1.0 



25.0 



20.0 



15.0 g 

 § 



-VD\ 



- 5.0 t 



6 



10 



12 Days 



Fig. 5. Growth responses in dba mice bearing 

 S-91 melanomas and exposed to different tem- 

 peratures. A, average (4 mice) volume of tu- 

 mors in mice exposed continuously to 40° C 

 ± I ° ; B, same as A but for mice held at 24° C 

 zt 2° (average of 4 tumors except 12th day 

 value based on 3) ; C, weight of mice held at 

 40° C minus respective tumor volumes X i.i 

 (= approx. wt. of host mouse) ; D, same as C 

 but for mice held at 24° C. Mice were main- 

 tained on Purina chow and water ad lib until 

 the gth day when they were also given whole- 

 wheat bread and water ad lib. 



Effect of temperature on tumor groivth 



That the high temperatures exert a marked effect on the general physiology of the 

 tumor (either directly or over host mechanisms) is evidenced by the pronounced 

 suppression of tumor growth. This is illustrated in Fig. 5 where the average tumor 

 volumes (Curves A and B) have been plotted against the approximate weights of the 

 host mice (Curves C and D). Table III illustrates the effect of exposure to 35° C on 

 tumor growth. While the host mice in the 40° C experiment (Fig, 5) were active and 

 vigorous at 12 days, tumor growth was markedly suppressed over this period following 

 an initial pronounced regression in volume (Curve 4). The experiment was discontinued 

 at 12 days. Other melanoma-bearing mice, maintained at 40° C for periods up to 10 

 days, behaved in a similar manner although detailed measurements of tumor size were 

 not taken. 



References p. 346. 



