Combined treatment with green tea catechins and sodium nitrite selectively promotes rat forestomach carcinogenesis after initiation with N-methyl-N′-nitro-N-nitrosoguanidine

Combined treatment with several phenolic antioxidants and sodium nitrite (NaNO2) has already shown to enhance rat forestomach carcinogenesis. In the present experiment, effects of green tea catechins (GTC) alone or in combination with NaNO2 on gastric carcinogenesis were investigated in a rat two-stage carcinogenesis model. Groups of eight, 6-week-old F344 male rats were given 0.01% N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in their drinking water and 5% NaCl in the diet for 10 weeks for glandular stomach initiation and a single intragastric administration of 100 mg/kg/bodyweight of MNNG at week 9 for forestomach initiation. From week 11, they received either drinking water containing 0.2% NaNO2 and a diet supplemented with 1% GTC in combination, each individual chemical alone or a basal diet until the end of week 42. In the forestomach, incidences and multiplicities of neoplastic lesions were clearly increased by the combined treatment, in spite of GTC alone suppressing the occurrence of papillomas. In a short-term experiment with similar protocol without MNNG pretreatment, a significant increase of 8-hydroxydeoxyguanosine (8-OHdG) levels in forestomach DNA occurred 24 h after the combined treatment, concomitant with erosion and inflammatory cell infiltration. In an in vitro study, electron spin resonance demonstrated hydroxyl radical formation after incubation of epigallocatechin gallate or epicatechin gallate with the NO generator, NOC-7. Thus, GTC alone showed a weak chemopreventive effect on forestomach carcinogenesis, but in the presence of NaNO2 it exerted a promotive effect which might involve hydroxyl-radical-associated oxidative DNA damage. However, no influence was exerted in the glandular stomach.