Effect of aging on EGF-stimulated replication of specific genes in rat hepatocytes.
EGF-stimulated replication of specific genes was examined in primary hepatocyte cultures from mature (6 months) and senescent (24 months) rats. Basal and EGF-stimulated [3H]thymidine incorporation and DNA polymerase alpha activities, as well as total cellular DNA, were also assessed. The genes examined were dihydrofolate reductase (DHFR) and c-myc, as well as total mitochondrial DNA (mt DNA). Although [3H]thymidine incorporation, DNA polymerase alpha activity, total cellular DNA, DHFR, and c-myc gene specific DNA replication stimulated by EGF are reduced with age, mt DNA replication is not affected by either EGF or age. Chromosomal DNA replication is mediated mainly by DNA polymerase alpha while mt DNA replication is mediated by its own DNA polymerase gamma. Thus, the age-related decline in stimulated DNA replication appears to be associated mainly with the DNA polymerase alpha activation pathway.
Kitano
S
S
Molecular Physiology and Genetics Section, Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging, Johns Hopkins Bayview Medical Center, Baltimore, Maryland 21224, USA.
Bohr
V A
VA
Reed
T D
TD
Haggerty
C M
CM
May
A
A
Roth
G S
GS
D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004256:DNA Polymerase I / Q000378:metabolism; D000074002:DNA Polymerase gamma; D004261:DNA Replication / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016259:Genes, myc / Q000235:genetics; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013936:Thymidine / Q000378:metabolism
D004272:DNA, Mitochondrial; D004815:Epidermal Growth Factor; D013762:Tetrahydrofolate Dehydrogenase; D004256:DNA Polymerase I; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D013936:Thymidine