Growth factor induced mitogenic effects and inositol phosphate responses in primary hepatocyte cultures from normal rat liver and rat liver nodules.
In our studies of normal and neoplastic growth regulation, we have compared growth factor induced second messenger response and mitogenic activity in a rat hepatocarcinogenesis model. Inositol phosphate (IP) turnover was measured by incubating the cells with [3H]inositol and stimulating them with either epidermal growth factor, diferric transferrin, ferricyanide, vasopressin, norepinephrine, angiotensin II or bombesin for 2 min. The IPs formed were separated on HPLC. Mitogenic responses were monitored by bromodeoxyuridine uptake and labeling index. IP turnover was stimulated by vasopressin, norepinephrine and angiotensin II in both normal and nodular cells, but not by the other four agonists tested. The IP response was somewhat lower in cells from liver nodules. All compounds except bombesin were mitogenic to both nodular cells and cells from normal rats of different ages, with epidermal growth factor inducing the largest mitogenic response. Bombesin, on the other hand, had only a minor effect on normal cells, but induced a pronounced mitogenic response in nodular cells. In normal rats, the cells' ability to respond to growth stimulation decreased with increasing rat age. In this respect, nodular cells behaved in a way more like young normal cells than their age-matched controls. Taken together, these data support the view of liver nodules being a more autonomous cell population, with increased sensitivity to growth factors and possibilities for autocrine growth stimulation.
Nilsson
H
H
Department of Pathology, Huddinge Hospital, Sweden.
Eriksson
L C
LC
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000819:agonists / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D008934:Mitogens / Q000494:pharmacology*; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006133:Growth Substances; D007295:Inositol Phosphates; D008934:Mitogens