Promotional effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) on N-nitrosobis(2-oxopropyl)amine (BOP)-initiated carcinogenesis in hamsters.
The effects of administration of low doses of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific nitrosamine, were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Female Syrian golden hamsters were given a single sc injection of BOP at a dose of 10 mg/kg and then administered 2 or 5 ppm NNAL in their drinking water for 52 wk. Additional groups of animals received the BOP injection alone, or only the 2 or 5 ppm NNAL treatments as BOP-negative controls. At wk 53 of the experiment, all surviving animals were killed and the development of proliferative lesions was assessed histopathologically. The total incidence of combined carcinomatous and dysplastic lesions of the exocrine pancreas was significantly higher (P < 0.05) in the BOP/NNAL 5 ppm group than in the BOP alone group, although there was no statistically significant influence of NNAL on the development of either pancreatic adenocarcinomas or dysplastic lesions viewed singly. The treatments with NNAL alone did not induce any proliferative lesions of the exocrine pancreas. No significant intergroup differences were found in either incidence or multiplicity of islet cell proliferative lesions. Immunohistochemical examination of islet cell proliferative lesions (hyperplasias and adenomas) found in the BOP-treated animals showed no significant differences in pancreatic hormone production between NNAL-treated and -untreated groups. The NNAL treatment did not exert any influence on lung, liver or kidney tumorigenesis. Thus, the results suggest that NNAL enhances BOP-induced exocrine but not endocrine pancreatic tumorigenesis in hamsters when given in the post-initiation phase.
Furukawa
F
F
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
Nishikawa
A
A
Enami
T
T
Mitsui
M
M
Imazawa
T
T
Tanakamaru
Z
Z
Kim
H C
HC
Lee
I S
IS
Kasahara
K
K
Takahashi
M
M
D000818:Animals; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004326:Drinking / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008647:Mesocricetus; D009602:Nitrosamines / Q000633:toxicity*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology
D002273:Carcinogens; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol