Organ-dependent modifying effects of oltipraz on N-nitrosobis(2-oxopropyl)amine (BOP)-initiation of tumorigenesis in hamsters.
5-(2-Pyrazinyl)-4-methyl-1,2-dithiole-thione (oltipraz), a substituted 1,2-dithiole-3-thione, is known to inhibit tumorigenesis induced by variety of carcinogens in several animal model systems. In the present experiment, the modifying effects of dietary oltipraz, given during N-nitrosobis(2-oxopropyl)amine (BOP) initiation of carcinogenesis, were investigated in Syrian hamsters. A total of 120 six-week-old females were divided into six groups. Groups 1-3 (30 animals each) were thrice given subcutaneous injections of BOP (10 mg/kg, body weight) at 1 week intervals and fed diets supplemented with 400 or 200 ppm of oltipraz or basal diet alone, starting 1 week prior and finishing 1 week after the carcinogen exposure. Groups 4-6 (10 animals each) were similarly treated without application of BOP. At the end of the 52nd experimental week, all surviving animals were autopsied and examined histopathologically for proliferative lesions of the major target organs for BOP tumorigenicity, including pancreas, liver, kidney, and lung. The incidences and multiplicity of adenocarcinomas of the pancreas were higher in groups 1 and 2 than in group 3 although without statistical significance. The incidence of pancreatic duct dysplasias was significantly (P<0.05) increased in group 2 (62.0%) but not in group 1 (50.0%) as compared with group 3 (46.6%). While the incidences of alveolar adenomas and carcinomas were significantly (P<0.05) decreased by the high dose, the multiplicities of hepatocellular adenomas, cholagiocellular carcinomas and gall bladder adenomas were elevated in the BOP/oltipraz groups (P<0.05). The results of the present study suggest that oltipraz exerts organ-dependent modifying effects on BOP-induced carcinogenesis in hamsters when given in the initiation stage.
Son
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Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan.
Nishikawa
A
A
Furukawa
F
F
Kasahara
K I
KI
Miyauchi
M
M
Nakamura
H
H
Ikeda
T
T
Hirose
M
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D005260:Female; D008647:Mesocricetus; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D009602:Nitrosamines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D013871:Thiones; D013876:Thiophenes
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D009602:Nitrosamines; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz; C031443:N-nitrosobis(2-oxobutyl)amine