Background: Intake of red meat is considered a risk factor for colorectal cancer (CRC) development, and heme, the prosthetic group of myoglobin, has been suggested as a potential cause. One of the proposed molecular mechanisms of heme-induced CRC is based on an increase in the rate of lipid peroxidation catalysed by heme.
Methods: In the present work, the novel A/J Min/+ mouse model for Apc-driven colorectal cancer was used to investigate the effect of dietary heme (0.5 μmol/g), combined with high (40 energy %) or low (10 energy %) dietary fat levels, on intestinal carcinogenesis. At the end of the dietary intervention period (week 3-11), spontaneously developed lesions in the colon (flat aberrant crypt foci (flat ACF) and tumors) and small intestine (tumors) were scored and thiobarbituric reactive substances (TBARS), a biomarker for lipid peroxidation was analysed in feces.
Results: Dietary hemin significantly reduced colonic carcinogenesis. The inhibitory effect of hemin was not dependent on the dietary fat level, and no association could be established between colonic carcinogenesis and the lipid oxidation rate measured as fecal TBARS. Small intestinal carcinogenesis was not affected by hemin. Fat tended to stimulate intestinal carcinogenesis.
Conclusions: Contradicting the hypothesis, dietary hemin did inhibit colonic carcinogenesis in the present study. The results indicate that fecal TBARS concentration is not directly related to intestinal lesions and is therefore not a suitable biomarker for CRC.
Keywords: Colorectal cancer; Heme iron; Intestinal carcinogenesis; Lipid peroxidation; Min mouse model; Red meat; TBARS.