Enhancement by isoproterenol of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.
The effect of isoproterenol on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and s.c. injections of isoproterenol or vehicle every other day for 13 weeks. Pre-neoplastic and neoplastic lesions staining positive for gamma-glutamyl transpeptidase (GGT) or the placental type of glutathione-S-transferase (GST-P) were examined histochemically at week 13. Prolonged administration of isoproterenol resulted in a significant increase in the number of GGT-positive, but not GST-P-positive, lesions. The incidence, number and size of hepatocellular carcinomas were also significantly greater in rats treated with isoproterenol than in controls. Administration of isoproterenol significantly increased the intracellular cAMP and the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that isoproterenol enhances hepatocarcinogenesis and that this may be related to its enhancing effect, mediated by cAMP, on cell proliferation in neoplastic lesions and surrounding hepatocytes.
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
H
H
Uehara
A
A
Nakaizumi
M
M
Baba
H
H
Iishi
M
M
Tatsuta
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D000242:Cyclic AMP / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D007545:Isoproterenol / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009602:Nitrosamines; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D004273:DNA, Neoplasm; D009602:Nitrosamines; C002741:N-nitrosomorpholine; D000242:Cyclic AMP; D007545:Isoproterenol