Carcinogenesis, Vol 19, 1417-1425, Copyright © 1998 by Oxford University Press
H Hikita, EF Nuwaysir, J Vaughan, K Babcock, MJ Haas, YP Dragan and HC Pitot
Previous work from this laboratory has reported on the effects of two
sequential 5 day periods of fasting and subsequent refeeding on tumor
promotion in multistage hepatocarcinogenesis in the rat (Carcinogenesis,
18, 159-166, 1997). In the present extension of the earlier study, the
sequential fasting-refeeding regimen was begun at later time points (28 and
54 days post-initiation) than the first study. This was done to determine
whether larger-sized altered hepatic foci (AHF) exhibited a depletion
similar to that of the relatively small AHF in the published experiment and
to study concomitant molecular changes during the fasting periods. Groups
of animals were fasted in the presence and absence of 0.05% phenobarbital
(PB) in the drinking water. During the fasting periods, both body and liver
weights decreased dramatically, less in the fast begun at 54 days. This
change was accompanied by a significant decrease in the bromodeoxyuridine
(BrdU) labeling indices of hepatocytes within AHF. Apoptotic bodies
increased dramatically in the non-focal (surrounding the AHF) hepatocytes
during the fasting periods. These parameters were slightly lower in
hepatocytes of rats administered PB during the fasting periods, most
notably during the 54-66 day period. With the nick end- labeling method,
the proportion of hepatocytes undergoing apoptosis was significantly higher
in cells within AHF at the end of each of the fasting periods in all but
one group. Concomitantly, the number of AHF and percentage of liver volume
occupied by AHF decreased dramatically during the fasting periods.
Refeeding caused a marked increase in BrdU labeling in hepatocytes within
and surrounding AHF during the first week or two, most notably in animals
not receiving PB during the fasting period. Both the number and volume
percentage of liver AHF returned to control values within approximately 2
weeks of the refeeding regimen. Assays of nuclear DNA fragmentation with
samples of whole liver indicated that a 'laddering' effect was most
noticeable in livers of animals subjected to the fasting-refeeding regimen
when phenobarbital was not present during the fasting period. Studies of
the levels of mRNA of several genes in the total liver revealed that the
expression of c-myc increased 3- to 9-fold during the fasting periods but
rapidly returned to normal levels after refeeding. Levels of albumin and
insulin-like growth factor I mRNAs decreased significantly during the
fasting period, but rapidly reappeared on refeeding. These results indicate
that the extensive loss of AHF during the short-term fasting periods occurs
even when the number and volume of AHF are 10- to 50-fold greater at the
beginning of the fast than the values published previously. Both the
decrease in insulin growth factor I and the elevation of c-myc expression
during the fasting period may indicate the role of these genes in the
transcriptional regulation of hepatocyte apoptosis in both normal and
preneoplastic hepatocytes in the rat.
ARTICLES
The effect of short-term fasting, phenobarbital and refeeding on apoptotic loss, cell replication and gene expression in rat liver during the promotion stage
McArdle Laboratory for Cancer Research, University of Wisconsin- Madison, 53706-1599, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Bursch, U. Wastl, K. Hufnagl, and R. Schulte-Hermann No Increase of Apoptosis in Regressing Mouse Liver after Withdrawal of Growth Stimuli or Food Restriction Toxicol. Sci., May 1, 2005; 85(1): 507 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Platz Energy Imbalance and Prostate Cancer J. Nutr., November 1, 2002; 132(11): 3471S - 3481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Berrigan, S. N. Perkins, D. C. Haines, and S. D. Hursting Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice Carcinogenesis, May 1, 2002; 23(5): 817 - 822. [Abstract] [Full Text] [PDF]
|
|