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. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=13410