344 ^^- WOODS, K. WIGHT, J. HUNTER, D. BURK VOL. 12 (1953) 



mutation become the continuing cause of self-perpetuating cellular abnormalities^^-^. 

 Very similar cellular abnormalities can also result from the action of viruses on mito- 

 chondrial development and function's. In the latter case, however, the continuing 

 presence of the virus is required since the mitochondria are not hereditarily changed. 

 Is it not possible that the lack of oxidative reserve, or conversely the glycolytic excess, 

 which characterizes the tumor ceU, may be the result of metabolic imbalance brought 

 about either by mitochondrial mutation, or by the action of a \anis on these organelles ? 

 Unfortunately, it has not yet been possible to subject animal mitochondria to genetic 

 tests as in the case of higher plants'". However, observations in mouse melanomas of 

 variable pigment content, while not conclusive, are at least consistent with the view that 

 mitochondria may act as genetic determiners in mammahan tumors^' ^^. Recently 

 Schneider et al.^, as a result of studies on carcinogenesis, have stated that " — the data 

 available at present support the concept that the mitochondria are involved in the 

 carcinogenic process in liver". The data from aberrant plant mitochondrial elements 

 suggest that similar modifications in homologous structures of animal cells could, from 

 the genetic standpoint, be the continuing cause of the respiratory defects and glycolytic 

 unbalance of malignant cells. 



The reactions of melanomas from mice exposed to high temperatures (40^ and 

 35° C) suggest that the capacity of the tumor to maintain a high rate of anaerobic 

 glycolysis may be dependent on the available supply of insulin. This is suggested by the 

 fact that the lowered (^co ^^ tumors from animals exposed to high temperatures for 

 only 13 to 20 hours (Table II) was raised by insuhn to levels characteristic of tumors that 

 had not been exposed to high temperatures. Thus one immediate result of exposure to 

 elevated temperature may be a reduction (absolute or relative) in the amount of insulin 

 in the tumor. This might be the result of a diminished blood circulation in the tumor 

 (this was evidenced by a decreased amount of blood in the excised tissues) , to decreased 

 secretion of the hormone, or to some combination of these and other factors (e.g. altered 

 pituitary function"' ^^. 



Since insulin has been reported to stimulate growth of hypophysectomized rats-" 

 it seems possible that this hormone might play a role in tumor growth. In view of the 

 marked effect of high temperature on melanoma growth and (^co^- it is of particular 

 interest to determine to what extent these factors may be interrelated. In this connection 

 it should also be noted that the apparent insulin deficiency of the heat-treated tumors 

 (as indicated by insulin-reversible lowering of Q^^J may be the expression of an in- 

 creased concentration of insulin-reversible glycolytic inhibitors such as have been 

 reported in the pituitary and adrenals'. Further experiments are in progress to determine 

 the extent and persistence of the temperature-induced growth suppression as well as 

 to further define the associated metaboHc changes and their relation to insulin. The 

 apparent critical relation between zinc and insulin concentrations with respect to <2c6, 

 is of general interest in connection with the mechanism of insulin action, but may also 

 have some special significance with respect to tumor metabolism. 



References p. 346. 



