Inhibition of benzo[a]pyrene-induced mouse forestomach neoplasia and reduction of H2O2 concentration in human polymorphonuclear leucocytes by flavour components of japanese-style fermented soy sauce

Previously it was reported that 4-hydroxy-2 (or 5)-ethyl-5 (or 2)-methyl-3(2H)-furanone (HEMF), a characteristic flavour component of Japanese-style fermented soy sauce that exhibits antioxidant activity, inhibits benzo[a]pyrene-induced forestomach neoplasia in mice. The antioxidant and anticarcinogenic activities of other structurally similar soy sauce flavour components are now reported. 4-Hydroxy-5-methyl-3(2H)-furanone (HMF) and 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) were found to be antioxidants. In particular, HMF and HDMF (as well as HEMF) reduced hydrogen peroxide concentration in human polymorphonuclear leucocytes stimulated by arachidonic acid or 12-O-tetradecanoylphorbol-13-acetate. HMF and HDMF were administered individually in semipurified diet to female ICR mice previously treated with benzo[a]pyrene (1.5 mg/wk, orally for 4 wk) to initiate forestomach neoplasia. The mice were killed at 30 wk of age. Both furanones reduced forestomach neoplasms, with HDMF exhibiting more potency. The data indicate that HDMF and HMF, like HEMF, inhibit carcinogenesis in this system by acting at the post-initiation stage.