Effects of low dose catechol on glandular stomach carcinogenesis in BALB/c mice initiated with N-methyl-N-nitrosourea.
The effects of low dose catechol administration in the diet on stomach carcinogenesis in mice after initiation with N-methyl-N-nitrosourea (MNU) in the drinking water were investigated. Male, 6-week-old, BALB/c mice were given MNU in the drinking water intermittently for 1-week periods at 1-week intervals for a total of 3 weeks at a concentration of 120 ppm (groups 1 and 3). Groups 2 and 4 served as non-initiated controls. From week 7, groups 1 and 3 were divided into four subgroups and the mice were fed on a diet containing 4 ppm (groups la and 3a), 20 ppm (groups 1b and 3b), 100 ppm (groups 1c and 3c), 500 ppm (groups 1d and 3d) or 0 ppm (groups 2 and 4) catechol for 44 weeks. At week 50, appreciably enhanced development of pepsinogen 1 altered pyloric glands (PAPG) was noted in groups 1c and 1d. The incidences of adenomatous hyperplasia and carcinomas were not affected in any of the catechol-treated groups as compared with corresponding controls on a basal diet. Thus, the administration of catechol in the diet at low doses enhanced only preneoplastic lesion development and not neoplastic lesion development. From these results, we conclude that the biological significance of the catechol promoting effect at probable human exposure levels on gastric cancer is probably limited, while the PAPG may be a sensitive endpoint lesion for mouse glandular stomach carcinogenesis.
Laboratory of Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
K
K
Kobayashi
K
K
Inada
C
C
Furihata
T
T
Tsukamoto
Y
Y
Ikehara
M
M
Yamamoto
M
M
Tatematsu
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002396:Catechols / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D020116:Pepsinogen A / Q000378:metabolism; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology
D002273:Carcinogens; D002396:Catechols; D008770:Methylnitrosourea; D020116:Pepsinogen A; C034221:catechol