404 4. ALLOXAN 



into cholesterol and fatty acids appears to be due primarily to the inter- 

 ference with acetate activation. The reason for the stimulation of oxygen 

 uptake and the source of the excess COg produced are not well understood. 



In the whole animal, the effects on liver lipids are complicated by the early 

 hyperglycemia and possible adrenal activation. When rats are injected 

 with 40 mg/kg alloxan intravenously there are increases of 7% and 63% 

 in total lipids and neutral fat, respectively, at 4 hr, but no changes occur 

 in phospholipids or cholesterol (Dury, 1954). Although these changes were 

 taken as evidence for a hepatotoxic action of alloxan, one would like to 

 have better evidence that these secondary factors are not actually respon- 

 sible. 



Nucleic Acid Metabolism 



Liver DNA is elevated in alloxan-diabetic rats. Since it was not known 

 whether this was due to the alloxan or to the diabetic state, Bass et al. 

 (1953) investigated the problem in greater detail. Alloxan was injected 

 intraperitoneally at a dose of 400 mg/kg and on the fifth day the DNA 

 in the liver had increased from 30.1 to 36.5 mg DNA-P/100 g, the RNA 

 level being unchanged. Pancreatectomy does not alter the liver DNA/RNA 

 ratio, although it to some extent increases both DNA and RNA. However, 

 the DNA per nucleus is not changed by pancreatectomy and is increased 

 by alloxan. It was concluded that the elevation of DNA is the result of 

 some specific direct effect of alloxan and is not related to the diabetic state. 

 It is not known if alloxan can in some manner stimulate DNA biosynthesis, 

 but it would seem unlikely. Harris (1963) showed that alloxan at 1 mM 

 inhibits rather strongly the incorporation of labeled uracil into the uridine 

 nucleotides in rat brain homogenates, and evidence was presented that 

 the major site of action is the phosphorylation of UMP to UDP. This has 

 been confirmed by noting the accumulation of uridine and UMP, and 

 eliminating other possible mechanisms (Younathan et al. 1963, 1964). 

 As far as I know, this is the only demonstrated action of alloxan on the 

 formation of nucleotides or nucleic acids. 



