Dietary Chlorella protects against heterocyclic amine-induced aberrant gene expression in the rat colon by increasing fecal excretion of unmetabolized PhIP

The food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines formed by cooking meat and fish at high temperature. PhIP induces colorectal adenoma risk in male rats when administered orally. This study used male Fisher 344 rats to investigate the impact of dietary Chlorella on PhIP metabolism and aberrant colonic gene expression following short-term PhIP treatment. High-performance liquid chromatography analysis revealed that fecal excretion of unmetabolized PhIP was significantly increased in rats whose diets were supplemented with Chlorella compared to rats in a PhIP-only group (P < 0.001). Quantitative realtime PCR confirmed that the increase in beta-catenin and cyclin D1 mRNA in the colon induced by PhIP was ameliorated in rats pre-fed with Chlorella (P = 0.052 for beta-catenin; P = 0.005 for cyclin D1). The increase in DNA shearing that is a hallmark of caspase-8-mediated apoptosis by PhIP was also significantly diminished in the colons of rats pre-fed Chlorella (P = 0.012). These results suggested that administering dietary Chlorella with a Western-style diet concomitantly or immediately before mutagen exposure might be beneficial in blocking the absorption of food mutagens such as PhIP.