ABSTRACT
Aflatoxin B1 (AFB1) when administered to partially hepatectomised rats 4 hr prior to sacrifice, activated the signalling pathway in regenerating rat liver. The activity of phosphatidylinositol (PI) kinase was found decreased at 30 min but increased at 24 hr and returned to normal at 48 hr. At 30 min, inositol-1,4,5-triphosphate (IP3) level increased significantly whereas diacylglycerol (DAG) level dropped. However, at 24 hr and 48 hr, DAG and IP3 showed the same trend i.e. an increase in their levels. Phosphatidylinositol-4-phosphate levels were found to increase at 24 hr. Protein kinase C (PKC), activity from the particulate fraction was significantly inhibited at 30 min, followed by increase in activity at 24 hr and return to normal at 48 hr. Cytosolic PKC showed a decrease at 24 hr and a significant increase at 48 hr. At the peak of DNA synthesis (24 hr) following partial hepatectomy, all these signalling steps had earlier been found to be inhibited, but the present study shows that aflatoxin B1 administration 4 hr prior to sacrifice reverses the action. Activation of PKC by aflatoxin B1, during regeneration of liver cells when PKC in normally inhibited, may possibly create conditions conducive to carcinogenesis.
Subject(s)
Aflatoxin B1/pharmacology , Animals , Hepatectomy , Liver/drug effects , Liver Regeneration/physiology , Male , Phosphatidylinositols/metabolism , Protein Kinase C/metabolism , Rats , Rats, Wistar , Signal Transduction/drug effectsABSTRACT
Phosphorylation of endogenous phosphatidylinositol was transiently increased following partial hepatectomy but was suppressed during peak DNA synthesis. Formation of inositol trisphosphate was decreased while generation of diacylglycerol and its breakdown to phosphatidic acid was increased. In response to partial hepatectomy protein kinase C was activated due to translocation from cytosol to particulate fraction, but the membrane bound activity was decreased during regeneration. Alteration of certain parameters in the signal transduction pathway apparently facilitates cell proliferation.