A comparison of ribonucleotide reductase activities in normal human fibroblast strains with their transformed counterparts.
The objective of this investigation was to examine the relationship between levels of ribonucleotide reductase activity and transformation of two human cell strains. Enzyme activity levels were elevated by 3.2- to 3.5-fold in transformed cells compared directly to the normal human fibroblast strains from which they were derived. There did not appear to be a general correlation between elevated ribonucleotide reductase and increased proliferation abilities as has been previously observed with some rodent tumor cell lines. In keeping with the rise in reductase activity, human transformed cells were relatively more resistant to the cytotoxic effects of hydroxyurea, an antitumor agent whose site of action is ribonucleotide reductase. This indicates that an important point to be considered during drug therapy aimed at the reductase, is the greater sensitivity of normal compared to transformed cells due to differences in enzyme activity. The results of this investigation support the view that an increased ability to reduce ribonucleotides is an important step towards the development of a neoplastic program in human cells.
D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000032:analysis*
D012264:Ribonucleotide Reductases; D006918:Hydroxyurea