Increasing development of pepsinogen-altered pyloric glands and adenocarcinoma in glandular stomach of analbuminemic rats.
The susceptibility of pepsinogen-altered pyloric glands (PAPG) and neoplastic glandular stomach lesions induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and catechol or sodium cholate in Nagase analbuminemic rats (NAR) was compared to Sprague-Dawley rats (SD). Male NAR and SD rats were given a single dose of 80 mg/kg body weight of MNNG by gastric intubation and, 2 weeks later, fed basal diet containing 0.8% catechol or 0.3% sodium cholate for 18 weeks. The animals were killed at the end of week 20 or after maintenance on basal diet at week 60. The number of pepsinogen-altered pyloric glands at week 20 was significantly (P < 0.001) higher in NAR fed either catechol or sodium cholate compared with SD rats. At week 60, adenomatous hyperplasias and adenocarcinomas were observed in 7 (88%; P < 0.01) and 3 (38%; P < 0.01) of 8 NAR fed catechol and in 4 (22%) and 0 of 18 SD rats, respectively. The results show that the frequency of PAPG in NAR and SD rats is related to the susceptibility to glandular stomach carcinoma. PAPG is a useful endpoint lesion for evaluation of gastric carcinogenicity in a 20-week carcinogenicity test, and NAR are sensitive for glandular stomach carcinogenesis.
Ogawa
K
K
First Department of Pathology, Nagoya City University Medical School, Japan.
Shichino
Y
Y
Tatematsu
M
M
Furihata
C
C
Asamoto
M
M
Nagase
S
S
Shirai
T
T
Ito
N
N
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D002273:Carcinogens; D002396:Catechols / Q000633:toxicity*; D019826:Cholic Acid; D002793:Cholic Acids / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006965:Hyperplasia; D008297:Male; D008769:Methylnitronitrosoguanidine; D010435:Pepsinogens / Q000378:metabolism*; D011706:Pyloric Antrum; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000172:deficiency* / Q000235:genetics; D013045:Species Specificity; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology*
D002273:Carcinogens; D002396:Catechols; D002793:Cholic Acids; D010435:Pepsinogens; D012709:Serum Albumin; D008769:Methylnitronitrosoguanidine; D019826:Cholic Acid; C034221:catechol