title: Signal transduction mechanism in response to aflatoxin B1 exposure: protein kinase C activity.
abstract: A single dose of the carcinogen aflatoxin B1 (7 mg/kg body weight) to male Wistar rats significantly enhanced the hepatic activity of protein kinase C in the particulate and nuclear fractions. The particulate fraction showed stimulation at 4 and 7 h, while the nuclear activity was increased at 17 h following administration of aflatoxin B1. The enzyme activity in cytosol revealed a significant decline corresponding to stimulation in particulate fraction. The carcinogen-activated protein kinase C stimulated autophosphorylation, and was found to accelerate in vitro phosphorylation of two model DNA synthesizing enzymes--the Klenow fragment of replicative DNA polymerase of E. Coli and a DNA primase-polymerase complex of yeast mitochondrial origin. Prior phosphorylation of these enzymes led to significant enhancement of their activities. The results imply that activation of protein kinase C and consequently the activation of DNA synthesizing enzymes may play an important role in the initiation of carcinogenesis.
authors.affiliation: Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Bombay, India.
authors.forename: K J
authors.initials: KJ
authors.lastname: Mistry
authors.forename: M
authors.initials: M
authors.lastname: Krishna
authors.forename: K
authors.initials: K
authors.lastname: Pasupathy
authors.forename: V
authors.initials: V
authors.lastname: Murthy
authors.forename: R K
authors.initials: RK
authors.lastname: Bhattacharya
mesh_terms: D016604:Aflatoxin B1 / Q000494:pharmacology*; D000818:Animals; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D004256:DNA Polymerase I / Q000378:metabolism; D019915:DNA Primase; D004591:Electrophoresis, Polyacrylamide Gel; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D012316:RNA Nucleotidyltransferases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016604:Aflatoxin B1; D011493:Protein Kinase C; D019915:DNA Primase; D012316:RNA Nucleotidyltransferases; D004256:DNA Polymerase I