Dose-dependent induction of glandular stomach preneoplastic and neoplastic lesions in male F344 rats treated with catechol chronically.
The dose-dependence of catechol glandular stomach carcinogenesis was investigated in male F344 rats. Groups of 30 male animals were fed catechol at dietary levels of 0 (control). 0.1, 0.2, 0.4, and 0.8% for up to 104 weeks. Five rats of each group were killed at 34 weeks and the remaining animals were sacrificed at the termination, all undergoing histopathological examination. Moderate retardation of body weight increase was observed in the 0.8% group. but no adverse effects were found in terms of survival. Submucosal hyperplasias and adenomas of the pyloric glands developed in the 0.4 and 0.8% groups, only very minor changes being noted in the 0.1 and 0.2% groups at week 34. Incidences of adenocarcinoma development in the pylorus were 4% and 8% in 0.4% and 0.8% groups, respectively, and 0 in the 0.1% and 0.2% groups, at the termination. Adenomas and submucosal hyperplasias were found in nearly all animals fed 0.2% catechol or more, the incidences of those in 0.1% group being 0% and 56%, respectively. Serum gastrin levels were significantly increased in the 0.2, 0.4, and 0.8% groups at 34 weeks, and in all treated groups at the termination, at extents comparable with the induction of proliferative lesions in the pylorus. The results thus demonstrated that dietary levels of 0.4% and 0.8% catechol long-term induce adenocarcinomas in the pyloric glands, while 0.1 and 0.2% cause benign proliferative lesions, all accompanied by increase in serum gastrin levels. As a no-effect level could not be decided in the present study, further investigation of lower doses is needed to determine whether a threshold exists.
Hagiwara
A
A
Daiyu-kai Institute of Medical Science, Ichinomiya, Japan. hagiwara@dims.be.to
Takesada
Y
Y
Tanaka
H
H
Tamano
S
S
Hirose
M
M
Ito
N
N
Shirai
T
T
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002396:Catechols / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D005755:Gastrins / Q000097:blood; D007150:Immunohistochemistry; D008136:Longevity / Q000187:drug effects; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology
D002396:Catechols; D005755:Gastrins; C034221:catechol