Consistent and fast inhibition of colon carcinogenesis by polyethylene glycol in mice and rats given various carcinogens

We have previously. shown that dietary polyethglene-glycol (PEG) suppresses the occurrence of azoxymethane-induced cancers in an accelerated rat model of colon carcinogenesis. To determine the consistency of this preventive e ffect, we carried out a long-term study in rats fed the standard American I nstitute of Nutrition 1976 diet, and 7 short-term prevention studies in rod ents, A total of 337 F344 rats, 20 Sprague Dawley rats, and 40 OF1 miff wer e all given initiating dose(s) of colon carcinogen, and were randomly alloc ated to experimental groups 7 d later. Treated groups received drinking wat er containing 5% PEG. After 30 or 162 d, the animals were examined for aber rant crypt foci or tumors in the colon. After two 20 mg/kg azoxymethane inj ections, the number of F344 rats with colon tumor was lower in rats receivi ng PEG for 161 d than in carcinogen-injected controls, 5/21 versus 25/27 (P < 0.0001). PEG-fed rats had no invasive cancer, and 10 times fewer colon t umors than controls (0.3 +/- 0.1 and 3.1 +/- 0.5 respectively. P < 0.0001). A three-day PEG treatment was sufficient to halve the number of azoxymetha ne-induced aberrant crypt foci in F334 rats (P = 0.0006), After 16 d of tre atment, PEG-fed rats had five times fen er foci than controls (21 +/- 14 an d 100 +/- 23 respectively, P < 0.0001), but the inhibition was reversible i n part when treatment was discontinued. Aberrant crypt foci initiated by N- methyl-N-nitrosourea intra-rectally (40 mg/kg) or by 2-amino-3,4-dimethyrim idazo(4,5-f)quinoline p.o. (2 x 200 mg/kg) were suppressed by PEG (P < 0.00 01 and P = 0.003 respectively). PEG was active in F344 rats, in Sprague Daw ley rats (P = 0.0005), and in OF1 mire (P = 0.001), PEGs with MW between 33 50 and 12000 (but not PEG 400) and PEG 8000 from five suppliers, markedly i nhibited azoxymethane-induced aberrant crypt foci (all P < 0.01). The preve ntion was stronger in rats fed a high-fat diet (P < 0.0001) than in rats fe d a rodent chow (P = 0.02). PEG was thus a fast, consistent, and potent inh ibitor of early colonic precursor lesions, Moreover, PEG is one of the most potent inhibitors of colon tumor in the standard rat model, Since PEG has no known toxicity in humans, we think it should be tested as a chemoprevent ive agent in a clinical trial.