Effect of N-phosphonacetyl-L-aspartate and D-glucosamine on the incorporation of 5-fluorouridine into normal tissues and an adenocarcinoma in the rat

Abstract

Cytostatic treatment of liver metastases from colorectal cancer has been of limited value. Higher drug levels in the target substances of the tumor may improve the results. It was the aim of this investigation to examine the effect of PALA (N-phosphonacetyl-L-aspartate) and D-glucosamine on the level of uracil nucleotides in the liver and in an N-methyl-N-nitrosoguanidine-induced adenocarcinoma of the colon transplanted to the liver of rats, and on the incorporation of 3H-FUrd into the acid-soluble fraction, the RNA and the DNA of the tumor and of several normal tissues. Combined treatment with PALA and D-glucosamine reduced the UTP pool in the liver and the tumor. D-glucosamine alone increased UDP-N-acetyl-hexosamine in liver tissue. Pretreatment with PALA and D-glucosamine increased incorporation of 3H-FUrd into RNA of the liver and kidney, and into the DNA fraction of the liver, but had no effect on 3H-FUrd incorporation in the tumor.