The metabolism of normal and tumour tissue

Abstract

Addition to the medium of [image]/1000 guanidine completely and reversibly inhibits the Pasteur effect in slices of rat brain cortex, the respiration continuing usually at a higher level while the aerobic (lactic) acid formation attains or exceeds the anaerobic. Complete restoration occurs on transference to guanidine-free medium. These effects are absent or less marked in other tissues and cells (amnion, medulla of kidney, Jensen sarcoma, baker''s yeast). Lower cones. (5 X 10"5 [image]) are ineffective. Methyl-guanidine acts like guanidine, but the dimethyl derivative shows little typical action. Glycocyamine, arginine and creatine (10-3 [image]) are toxic; agmatin causes a slow inhibition of the Pasteur effect. Biuret (10-3 [image]) and [image]/50 urea and acetamide have no action on respiration or glycolysis. Certain substituted guanidines and amidines are the most powerful inhibitors of the Pasteur effect yet described: these are 1 :ll-undecanediamidine and decamethylenedi-guanidine (Synthalin), which are fully active at 10-6-10-5 [image]; the precise concentration depending on the relative amounts of solution and tissue. Both are powerful trypanocides; other specific antiseptics of the acridine and quinoline series have previously been found to inhibit the Pasteur effect in brain. This property is not however shared by all trypano cides, for Bayer 205 (10-4 [image]) and Trypan blue (10-3 [image]) do not affect brain metabolism. Decamethylenedmothiourea causes an incomplete inhibition of the Pasteur effect. The bearing of these results on the mechanism of the Pasteur effect, and the possibility of their connection with tetany and specific antisepsis are discussed.