From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Tue Mar 21 2000 - 01:10:01 MST
Citations: 1-3 (plus an additional note.)
<1>
Authors
Parnaud G. Tache S. Peiffer G. Corpet DE.
Institution
Securite des Aliments, Institut National de la Recherche Agronomique, Ecole
Nationale Veterinaire de Toulouse, France.
Title
Polyethylene-glycol suppresses colon
cancer and causes dose-dependent regression of
azoxymethane-induced aberrant crypt foci in rats.
Source
Cancer Research. 59(20):5143-7, 1999 Oct 15.
Abstract
Dietary polyethylene-glycol (PEG) 8000, a
nonfermented polymer laxative, strongly suppresses azoxymethane-induced
aberrant crypt foci (ACF) in the colon of rats, as shown in a previous study
(D. E. Corpet et al., Carcinogenesis (Lond.), 20: 915-918, 1999). In the
present study, we tested the effect of PEG administered during either
initiation or postinitiation, the dose-response effect of PEG, the regressive
effect of PEG on established ACF, and the preventive effect of PEG on colon
cancers in rats. The general design was to initiate
carcinogenesis in F344 rats by a single injection of azoxymethane (20 mg/kg)
and to randomize the animals 7 days later to AIN-76 diets containing 5% PEG
or no PEG (control). At termination, ACF and tumors were scored blindly by a
single observer. The administration of 5% PEG for 32 days to groups of 10
female rats in either food or drinking water reduced the number of ACF by a
factor of 8 (P = 0.0002) and reduced the number of large ACF by a factor of
20-30 (P = 0.002). No protection was afforded when PEG was given only during
the initiation phase. Diets containing 0%, 0.5%, 2%, or 5% PEG fed for 35
days to four groups of male rats inhibited ACF in a dose-dependent manner (P
< 0.0001). The administration of a 5% PEG diet for 41 days, starting 42 days
after carcinogen injection, led to a 73% decrease in the number of ACF (P <
0.0001). Dietary PEG thus caused the regression of established ACF.
Macroscopic tumors were evaluated by histology in rats that had been fed a
high-fat diet containing cooked casein to promote tumor growth for 81 days.
In this accelerated model of carcinogenesis, dietary PEG suppressed the
occurrence of colon adenomas and carcinomas: the incidence of tumors
decreased from 70% to 10% (P = 0.005); and the multiplicity decreased from
2.1 to 0.1 tumor(s)/rat (P = 0.003). No cancer was detected
in the PEG-fed rats. Taken together, these results suggest that PEG could be
a potent anticancer agent in the postinitiation phase of
carcinogenesis. Because PEG is a substance that is generally recognized as
safe (GRAS list, Food and Drug Administration), its
cancer-preventive features could be tested in humans.
<2>
Authors
Corpet DE. Parnaud G.
Institution
Securite des Aliments, INRA, Ecole Nationale Veterinaire de Toulouse, France.
d.corpet@envt.fr
Title
Polyethylene-glycol, a potent suppressor of
azoxymethane-induced colonic aberrant crypt foci in rats.
Source
Carcinogenesis. 20(5):915-8, 1999 May.
Abstract
Bulking fibers and high water intake may decrease colon carcinogenesis in
rats, and the risk of colorectal cancer in humans. We
speculated that a non-fermented polymer,
polyethylene-glycol (PEG) 8000, which
increases stool moisture, might protect rats against colon carcinogenesis.
Thirty female F344 rats were given a single injection of azoxymethane (20
mg/kg), and 7 days later randomized to AIN76 diets containing PEG (to provide
3 g/kg body wt/day), or no PEG (control). Diets were given ad libitum for 105
days, then colon carcinogenesis was assessed by the aberrant crypt foci (ACF)
test. ACF were scored blindly by a single observer. Dietary feeding of PEG
almost suppressed ACF larger than one crypt, and strikingly decreased the
total number of ACF per rat. PEG-fed rats had 100 times less large ACF than
controls (0.8 and 83 respectively, P = 0.00001). PEG-fed rats had 20 times
less total ACF than control (six and 107 ACF/rat, respectively; P < 0.0001).
Two treated rats had no detectable ACF. PEG is 10 times more potent than
other chemopreventive agents in this model. Since PEG is generally recognized
as safe, its cancer-preventive features could be tested in
humans.
<3>
Authors
Laboisse CL. Maoret JJ. Triadou N. Augeron C.
Institution
Laboratoire de Biologie et de Physiologie des Cellules Digestives (U239
I.N.S.E.R.M.), Faculte X. Bichat, Paris, France.
Title
Restoration by polyethylene glycol of
characteristics of intestinal differentiation in subpopulations of the human
colonic adenocarcinoma cell line HT29.
Source
Cancer Research. 48(9):2498-504, 1988 May 1.
Abstract
The human colonic cancer cell line HT29 is morphologically
undifferentiated in standard culture conditions. The cells were incubated for
30 s in polyethylene glycol (27%, v/v),
then washed, and refed with standard medium. In these conditions of
treatment, polyethylene glycol was unable
to induce a significant cell multinucleation. Three wk after the treatment,
circular "flat-foci" developed in the culture, which consisted of circular
monolayers of polarized cells. These subpopulations were isolated, then grown
as independent lines (lines 27, 28, 30, and 31) in standard culture
conditions, and characterized. Two types of differentiated cells were present
in these lines, namely, enterocytic cells and mucus-secreting goblet cells.
These characteristics of intestinal differentiation were found to be stable
during the long-term culture of these lines in standard medium. We were able
to isolate from line 27 a clonal derivative (C1.27H) exhibiting 2 lineages of
differentiation, as assessed by electron microscopy, immunofluorescence, and
immunoblot analysis of cell membranes with anti-sucrase-isomaltase
antibodies, and enzyme activities. Sucrase-isomaltase was present in two
forms, namely, the high-molecular-weight precursor and the cleaved subunits.
Finally, the C1.27H cells were found to be significantly less tumorigenic
than the parental HT29 cells in both in vitro and in vivo tumorigenicity
tests. This stably differentiated cell clone could represent the
cancer derivative of the normal stem cells of the intestinal
crypt. It is therefore a possible model system for the study of intestinal
cell differentiation.
Additional note by poster:
High molecular weight peg 8000 appears to be useful in the treatment
of colon cancer. Considering its very high safety margins relative
to conventional chemotherapy, it deserves first consideration for
further research. (too bad it is not patentable!)
The question I would like to see addressed is whether low
molecular weight peg 200 could be useful in the treatment of other
cancers. Since this would be absorbable from the gastrointestinal
tract, it might be active against a wide variety of tumors.
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