Different growth capacity between infant and adult mouse hepatocytes in vitro correlates to the cyclin D1 level without relation to oxidative DNA damage.
BACKGROUND
Proliferating capacity of hepatocytes is rapidly decreased during growth into maturity, but its exact reason(s) are not well known.


METHODS
Hepatocytes isolated from infant (10-14 days old) and adult (10-13 months old) B6C3F1 mice were cultivated in the medium containing epidermal growth factor and insulin. Proliferative capacity, apoptosis, morphological changes, cell cycle proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were compared between the two hepatocyte populations.


RESULTS
Although adult hepatocytes rapidly underwent cellular crisis characterized by extended morphology and multiple nuclei without proliferation, infant hepatocytes could proliferate with less crisis. Cyclin D1 was much more abundant in the infant than adult cells, but there was no difference according to the expression of cdk4, cdk2, cyclin E and cdk inhibitors (p16(Ink4) (p16), p21(Cip1/Waf1) (p21) and p27(Kip1) (p27)). 8-OHdG became high soon after cultivation, while it rapidly went down after day 2 both in the infant and adult cells.


CONCLUSIONS
The high growth capacity of infant hepatocytes in vitro was dependent on the cyclin D1 level, but there was no relation to 8-OHdG.
Imamura
Emi
E
Department of Pathology, Asahikawa Medical College, 2-1-1-1 East Midorigaoka, Asahikawa 078-8510, Japan.
Yamamoto
Masahiro
M
Miyakoshi
Masaaki
M
Honmo
Satoshi
S
Ozaki
Atsuko
A
Yoshie
Masumi
M
Tamakawa
Susumu
S
Yaginuma
Yuji
Y
Kasai
Shinichi
S
Ogawa
Katsuhiro
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000032:analysis*; D019927:Cyclin E / Q000032:analysis; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction
D019927:Cyclin E; D019938:Cyclin D1; D000080242:8-Hydroxy-2'-Deoxyguanosine; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D003849:Deoxyguanosine