Chemopreventive activity of oltipraz against induction of glandular stomach carcinogenesis in rats by N-methyl-N'-nitro-N-nitrosoguanidine.
The modifying effects of oltipraz on induction of glandular stomach carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in a total of 120 male 6-week-old Wistar rats, divided into six groups. Groups 1-3 (30 animals each) were given 100 p.p.m. MNNG in their drinking water for 10 weeks as an initiation treatment for gastric cancer induction and respectively fed diets supplemented with 0.04%, 0.02% and 0% oltipraz for 12 weeks, starting 1 week before and finishing 1 week after the carcinogen exposure. Groups 4-6 (10 animals each) were similarly treated without the application of MNNG. At the end of the 80th experimental week, all surviving animals were autopsied and examined histopathologically for the existence of gastric proliferative lesions. The incidence and multiplicity of adenocarcinomas were significantly (P < 0.01) lower in group 1 than in group 3. In addition, the multiplicity of atypical hyperplasias in the pyloric region was significantly (P < 0.05) decreased in group 1 as compared with the group 3 value. No gastric proliferative lesions were found in groups 4-6. In an additional short-term experiment, oltipraz significantly reduced cell proliferative activity (P < 0.01) and elevated glutathione levels (P < 0.05) in the glandular stomach mucosa of rats treated with MNNG. Thus our results clearly indicate that oltipraz can inhibit induction of proliferative glandular stomach lesions by MNNG in the rat.
Nishikawa
A
A
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. nishikaw@nihs.go.jp
Tanakamura
Z
Z
Furukawa
F
F
Lee
I S
IS
Kasahara
K
K
Ikezaki
S
S
Takahashi
M
M
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D006965:Hyperplasia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008769:Methylnitronitrosoguanidine; D011708:Pylorus / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013871:Thiones; D013876:Thiophenes
D016588:Anticarcinogenic Agents; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D008769:Methylnitronitrosoguanidine; C026209:oltipraz