Dietary phytate lowers - mutational frequency, decreases DNA-adduct and hydroxyl radical formation in azoxymethane-induced colon cancer.

OBJECTIVES

Dietary phytate is known to protect against azoxymethane (AOM)-induced preneoplastic lesions. The present study was designed to determine whether dietary phytate affects mutation frequency in colon epithelial cells challenged with azoxymethane , through lowering the formation of O-methyl guanosine (O-MeG) and 8-hydroxy deoxyguanosine (8-OHdG) adducts.

MATERIALS AND METHODS

We used Fisher F344 rats induced with AOM for 20 weeks and undertook 1% or 2% phytate supplementation for subsequent 16 weeks to monitor the mutation frequencies of one of the candidate genes, K-, along with DNA adduct load.

RESULTS

Dietary phytate significantly suppressed aberrant crypt foci formation and effectively inhibited colon tumor formation in a dose-dependent manner. DNA sequencing results demonstrated that 60% of the colon tumors from AOM-treated and control diet fed animals showed GGT to GAT transition and 40% of the tumors showed GGT to GTT transversion at codon 12, along with 18% of the tumors showing GGC to CGC transversion at codon 13. Phytate supplementation at 1 and 2% lowered the frequency of GGT > GAT to 30 and 10%, respectively. Phytate supplementation also nullified the codon 13 mutations. No mutations were observed at codon 61 in any of the experimental groups.

CONCLUSION

The lowered frequency of K- mutations correlated with decreased formation of hydroxyl radicals, O-meG and 8-OH-dG levels in phytate-supplemented animals with lowered tumor burden.