Inhibition of ribonucleotide reductase in thymocytes of rats treated by ditiocarb sodium.
The i.p. administration of ditiocarb sodium (diethyldithiocarbamate, DDC) at doses of 500 and 1000 mg/kg body wt. decreased within 1 h and in a competitive manner the ribonucleotide reductase (RNR) activity of rat thymocytes by about 25 and 40%, respectively. Under the same conditions, scheduled DNA synthesis was inhibited by almost 30 and 75%, whereas RNA synthesis remained unchanged. 1000 mg DDC/kg body wt. resulted in a long-lasting diminution in thymus weight; the spleen revealed no significant drug effects. It is suggested that the decrease of RNR activity in thymocytes of DDC-treated rats is a major determinant in the (reversible) inhibition of DNA synthesis which, in turn, may be implicated in the radio- and chemoprotective effects of the drug.
Tempel
K
K
Institut für Pharmakologie, Toxikologie und Pharmazie, Tierärztlichen Fakultät, Universität, Munich, Fed. Rep. of Germany.
Spath
A
A
Stammberger
I
I
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004050:Ditiocarb / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D009929:Organ Size / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects
D012313:RNA; D004247:DNA; D004050:Ditiocarb; D012264:Ribonucleotide Reductases