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.
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