Effect of aflatoxin B-1 on phosphoinositide signal transduction pathway during regeneration of liver cells following partial hepatectomy

Aflatoxin B-1 (AFB(1)) when administered to partially hepatectomised rats 4 hr prior to sacrifice, activated the signalling pathway in regenerating ra t liver. The activity of phosphatidylinositol (PI) kinase was found decreas ed 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 wherea s 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. Phosphatidylino sitol-4-phosphate levels were found to increase at 24 hr. Protein kinase C (PKC), activity from the particulate fraction was significantly inhibited a t 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 hepatecto my, all these signalling steps had earlier been found to be inhibited, but the present study shows that aflatoxin B-1 administration 4 hr prior to sac rifice reverses the action. Activation of PKC by aflatoxin B-1, during rege neration of liver cells when PKC in normally inhibited, may possibly create conditions conducive to carcinogenesis.