THE SEQUENTIAL-ANALYSIS OF LIVER-CELL NECROSIS - INHIBITION OF DIETHYLNITROSAMINE-INDUCED AND DIMETHYLNITROSAMINE-INDUCED ACUTE LIVER-CELL DEATH BY POST-TREATMENT WITH DIETHYLDITHIOCARBAMATE

Google Scholar
  • 1 January 1980
    • journal article
    • research article
    • Vol. 99  (1) , 159-+
Abstract
Posttreatment with diethyldithiocarbamate (DEDTC) largely prevented the development of acute hepatocellular necrosis induced by diethylnitrosamine (DEN) and dimethylnitrosamine (DMN) [carcinogens] in male Fischer rats as monitored by the release of glutamate-pyruvate transaminase and sorbitol dehydrogenase into the serum and by histologic examination. Liver cell necrosis was evident with a dose of 25 mg of DEN/kg and was progressive with increasing doses of DEN. DEDTC (50 mg/kg; 3 times at 4-h intervals) was given at 4 or 8 h after the administration of DEN (100 mg/kg), time points at which at least 50% and 75%, respectively, of the administered DEN had disappeared from both the serum and liver. Under these conditions, DEDTC prevented liver cell necrosis, except for a few isolated single cells. Similar inhibition was also observed when DEDTC was given 4 h after the administration of a necrogenic dose of DMN (20 mg/kg). DEDTC, when administered 4 h after DEN, delayed the rate of clearance of DEN and of ethylation of DNA and RNA but did not significantly affect the total extent of ethylation of rat liver nucleic acids. These results offer further support for the multistep hypothesis for the development of liver cell necrosis.