X-Message-Number: 13410
Date: Tue, 21 Mar 2000 00:09:35 -0800 (PST)
From: Doug Skrecky <>
Subject: peg - a non-toxic treatment for colon cancer

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.
  
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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