Differential effects of 4-hydroxyaminoquinoline-1-oxide on pancreatic and liver DNA synthesis in rats.
The effect of 4-hydroxyaminoquinoline-1-oxide (4-HAQO) on DNA synthesis in the pancreas and liver, target and non-target organs for 4-HAQO carcinogenesis, respectively, were compared. Pancreatic and liver DNA synthesis were simultaneously induced in rats fed a protein deficient diet containing 0.5% DL-ethionine for 18 days, and DNA synthesis in both tissues was inhibited by hydroxyurea. A single i.v. injection of 4-HAQO at a dose of 7 mg/kg body weight also inhibited DNA synthesis in both tissues within 4 h. In the pancreas the inhibition was maximum at a dose of 7 mg/kg, and DNA synthesis was less than in the pancreas of rats fed a control grain diet. This inhibition continued for the subsequent 5 days which were tested. In the liver, the degree of inhibition was less than in pancreas but the value remained higher than in rats fed control diet. The inhibition of liver DNA synthesis at a dose of 7 mg/kg completely recovered within 1 day. These results suggest that the lesions of DNA induced by 4-HAQO and its repair might be different between the pancreas and the liver. A pancreatic chemical carcinogen, 4-HAQO, might thus have the same cytotoxic effect that liver carcinogens have toward the liver resulting in failure to respond to mitotic stimuli. This might be causally related to the organotropism of 4-HAQO toward the pancreas.
D015108:4-Hydroxyaminoquinoline-1-oxide / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D004044:Dietary Proteins; D005001:Ethionine / Q000494:pharmacology; D006918:Hydroxyurea / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D000634:Aminoquinolines; D004044:Dietary Proteins; D015108:4-Hydroxyaminoquinoline-1-oxide; D004247:DNA; D005001:Ethionine; D006918:Hydroxyurea