Signal transduction mechanism in response to aflatoxin B1 exposure: protein kinase C activity.
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.
Mistry
K J
KJ
Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Bombay, India.
Krishna
M
M
Pasupathy
K
K
Murthy
V
V
Bhattacharya
R K
RK
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*
D016604:Aflatoxin B1; D011493:Protein Kinase C; D019915:DNA Primase; D012316:RNA Nucleotidyltransferases; D004256:DNA Polymerase I