Methionine restriction inhibits colon carcinogenesis

Area of Science:

• Oncology
• Nutritional Science
• Gastroenterology

Background:

• Previous studies demonstrated that life-long methionine restriction (MR) in rats increases lifespan and inhibits aging-related diseases.
• Aberrant crypt foci (ACF) are preneoplastic lesions in the colon and are considered early indicators of colorectal cancer development.

Purpose of the Study:

• To investigate the effects of methionine restriction (MR) on the formation of preneoplastic aberrant crypt foci (ACF) in the colon of azoxymethane (AOM)-treated rats.
• To determine if MR influences colonic cell proliferation.

Main Methods:

• Six-week-old male F344 rats were fed either a control diet (0.86% methionine) or an MR diet (0.17% methionine).
• Rats were administered azoxymethane (AOM) for two consecutive weeks.
• Aberrant crypt foci (ACF) formation and colonic cell proliferation were assessed 10 weeks after AOM treatment.

Main Results:

• Methionine restriction (MR) markedly reduced ACF formation by over 80% compared to controls (P < 0.001).
• A similar significant reduction in ACF was observed when MR was applied only during the post-initiation period (P < 0.001).
• MR led to a 12% reduction in colonic cell proliferation (P < 0.05).

Conclusions:

• Methionine restriction (MR) inhibits colonic tumor development in rats.
• The inhibitory effect of MR on colon carcinogenesis occurs primarily during the post-initiation phase.
• Inhibition of colonic cell proliferation may be a key mechanism underlying the anti-cancer effects of MR.