Methionine restriction inhibits colon carcinogenesis.
Previously, we demonstrated that life-long methionine restriction (MR) in rats increases life span and inhibits aging-related disease processes. The present study examines the effects of MR on the formation of preneoplastic aberrant crypt foci (ACF) in the colon of azoxymethane (AOM)-treated rats. Six-week-old male F344 rats were placed on essential amino acid-defined diets containing either 0.86% Met (control diet) or 0.17% Met (MR diet) and 1 wk later were given AOM (15 mg/kg/wk, s.c.) for 2 consecutive wk. Ten weeks after the final AOM treatment, ACF formation was markedly reduced in rats fed the MR diet with ACF containing > or = 4 crypts/focus being reduced by over 80% compared to controls (P < 0.001). A similar 83% reduction in ACF containing > or = 4 crypts/focus was observed in rats fed the MR diet only during the post-initiation period (after the final dose of AOM; P < 0.001). Five weeks after AOM administration, a 12% reduction in colonic cell proliferation was observed in MR rats compared to controls (P < 0.05). These results show that MR inhibits colonic tumor development in the rat, an effect that occurs primarily during post-initiation phases of carcinogenesis and may be due, in part, to an inhibition of colonic cell proliferation.
Komninou
Despina
D
Institute of Cancer, Valhalla, NY 10595, USA.
Leutzinger
Yvonne
Y
Reddy
Bandaru S
BS
Richie
John P
JP
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D001681:Biological Assay; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000172:deficiency*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D008715:Methionine; D001397:Azoxymethane