Document Detail

Enhanced thyroid carcinogenicity of N-nitrosobis(2-oxopropyl)amine in Otsuka Long-Evans Tokushima Fatty rats, a model of type II diabetes mellitus.
MedLine Citation:
PMID:  17510084     Owner:  NLM     Status:  MEDLINE    
Epidemiologic data suggest that diabetes mellitus type II is a risk factor for several types of cancer, including pancreatic, liver, colon and thyroid cancers. In the present study, effects of diabetes/hyperlipidemia on N-nitrosobis(2-oxopropyl)amine (BOP)-induced cancer development were examined in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, model animals for non-insulin-dependent diabetes mellitus and Long-Evans Tokushima Otsuka (LETO) rats, appropriate controls. Males of both strains were given four subcutaneous injections of BOP (10 mg/kg body wt) or saline on alternative days, starting at 5 weeks of age. BOP induced tumors in a variety of tissues, including the thyroid gland, colon, kidney, liver and lung. The highest yields were noted for thyroid tumors, the incidence (P = 0.0182) and multiplicity (P < 0.001) of BOP-induced thyroid cancers with marked fibrosis being significantly higher in OLETF than in LETO rats. Interestingly, anaplastic thyroid carcinomas were observed limited to the BOP-treated OLETF rats. Additionally, a greater incidence and frequency of aberrant crypt foci, putative precursor lesions for colon tumors, was observed in the BOP-treated OLETF group. However, BOP was ineffective at inducing pancreatic ductal tumors. No thyroid, liver, lung or colon tumors were found in the OLETF and LETO rats receiving the vehicle. Significant increases in serum levels of insulin, glucose, phospholipids, triglycerides and total cholesterol were detected in the OLETF rats compared with the LETO rats, regardless of the treatment. Our results indicate that diabetic/hyperlipidemic state can enhance BOP-induced carcinogenesis of the thyroid gland and to a lesser extent the colon in OLETF rats.
Katsuhisa Sakano; Mami Takahashi; Michihiro Mutoh; Naoko Niho; Masami Komiya; Hidetaka Sato; Takuji Tanaka; Takashi Sugimura; Keiji Wakabayashi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-16
Journal Detail:
Title:  Carcinogenesis     Volume:  28     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-08     Completed Date:  2007-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  2193-8     Citation Subset:  IM    
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
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MeSH Terms
Carcinogens / administration & dosage,  toxicity*
Colonic Neoplasms / chemically induced,  pathology
Diabetes Mellitus, Type 2 / complications*,  genetics
Injections, Subcutaneous
Nitrosamines / administration & dosage,  toxicity*
Rats, Inbred OLETF
Rats, Long-Evans
Risk Factors
Species Specificity
Thyroid Neoplasms / chemically induced*,  pathology
Reg. No./Substance:
0/Carcinogens; 0/Nitrosamines; 60599-38-4/nitrosobis(2-oxopropyl)amine

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