Dose-dependent promoting effects of catechol on glandular stomach carcinogenesis in BALB/c mice initiated with N-methyl-N-nitrosourea

The effects of catechol administration in the diet on stomach carcinogenesis in mice after initiation with N-methyl-N-nitrosourea (MNU) in the drinking water were investigated in a development trial for a new experimental protocol. Male 6-week-old BALB/c mice were given MNU in the drinking water intermittently for a total of three one-week periods, with one-week intervals, at the concentration of 120 ppm (groups 1 and 2), Groups 3 and 4 served as non initiated controls. From week 7, groups 1 and 3 were divided into three subgroups and the mice were fed on diet containing 0.05% (groups 1a and 3a), 0.2% (groups 1b and 3b), 0.8% (groups 1c and 3c) or 0% (groups 2 and 4) catechol for 29 weeks. At week 20, appreciably enhanced development of pepsinogen 1-altered pyloric glands was noted in all catechol-treated groups, in a partially dose-dependent manner (12.8 ± 12.5, 13.8 ± 11.7, and 24.0 ± 12.7/100 pyloric glands respectively, for groups 1, 2 and 3). The incidences of adenomas (groups 1, 2 and 3) were also increased. At week 35, dose-dependent induction of adenocarcinomas in groups 1 (3/19), 2 (3/19) and 3 (14/20) was evident. In addition, the depth of invasion of the adenocarcinomas was enhanced by catechol in a dose-dependent manner, though the histological type was not influenced. Thus, the administration of catechol in the diet strongly enhanced the preneoplastic and neoplastic lesions in mouse glandular stomach induced by MNU in the drinking water, in a dose-dependent manner.