Mitogen-induced liver hyperplasia does not substitute for compensatory regeneration during promotion of chemical hepatocarcinogenesis.
Experiments were designed to determine the efficacy of different types of liver cell proliferative stimuli given during exposure to several liver tumor-promoting regimens, on the formation of foci of enzyme-altered hepatocytes. Male Wistar rats were initiated with diethylnitrosamine (150 mg/kg body wt). After a 2 week recovery period animals were subjected to promoting regimens, the resistant hepatocyte model, the phenobarbital model and the orotic acid model. While the rats were on these regimens they were given liver cell proliferative stimulus, either a compensatory type (two-thirds partial hepatectomy or a necrogenic dose of carbon tetrachloride) or a direct hyperplastic stimulus such as that induced by the primary mitogen, lead nitrate. Initiated cells so promoted by these regimens were monitored as foci of enzyme-altered hepatocytes positive for gamma-glutamyltransferase and placental glutathione S-transferase or deficient for adenosine triphosphatase. While carbon tetrachloride and partial hepatectomy-induced compensatory regeneration stimulated the promoting ability of the regimens used, direct hyperplasia could not stimulate the formation of foci and/or nodules from initiated hepatocytes. Evaluation of thymidine incorporation indicated that there was no significant difference in the extent of DNA synthesis in both the proliferative stimuli irrespective of the promoting procedure used.
Ledda-Columbano
G M
GM
Istituto di Patologia Sperimentale, Cagliari, Italy.
Coni
P
P
Curto
M
M
Giacomini
L
L
Faa
G
G
Sarma
D S
DS
Columbano
A
A
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity*; D006965:Hyperplasia / Q000139:chemically induced; D007854:Lead / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008115:Liver Regeneration; D008297:Male; D009566:Nitrates / Q000633:toxicity*; D009963:Orotic Acid / Q000633:toxicity*; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase
D009566:Nitrates; D007854:Lead; D004052:Diethylnitrosamine; D009963:Orotic Acid; C017461:lead nitrate; D015073:2-Acetylaminofluorene; D002251:Carbon Tetrachloride; D005723:gamma-Glutamyltransferase; D010634:Phenobarbital