Molecular Aspects during Multi-step Chemical Induced Carcinogenesis in the Lung and Pancreas

Tsujiuchi, Toshifumi; Tsutsumi, Masahiro; Konishi, Yoichi

doi:10.1293/tox.16.133

Cited by 3 publications

(3 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pancreatic carcinogenesis is known to be a multi-step process involving multiple genetic alterations in humans [34-37] and similar genetic alterations have been found in hamsters [38,39]. Findings for genetic alterations in pancreatic ductal cancers in the two species are summarized in Table 1.…”

Section: Genetic Alterations In Pancreatic Ductal Carcinomas Of Humanmentioning

confidence: 91%

Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

Takahashi

Hori

Mutoh

et al. 2011

Cancers

View full text Add to dashboard Cite

Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

show abstract

Section: Genetic Alterations In Pancreatic Ductal Carcinomas Of Humanmentioning

confidence: 91%

Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

Takahashi

Hori

Mutoh

et al. 2011

Cancers

View full text Add to dashboard Cite

show abstract

“…23 In constrast with their scant chemistry 24−26 since Thiele's pioneering work, the biological interest in this class is burgeoning. 27,28 We recently demonstrated some of their potential by isolating and characterizing the first nitrosocarbamides complexes (F). 29,30 Among the unusual hydrolysis and degradation products of F is the release of nitrous oxide, which is attributed to the intermediacy of nitroxyl anions, NO − .…”

Section: ■ Introductionmentioning

confidence: 99%

“…Perhaps the best understood set of derivatives, the nitrosocarbamates ( E ), was first described by Joachim Thiele in 1898 . In constrast with their scant chemistry − since Thiele’s pioneering work, the biological interest in this class is burgeoning. , We recently demonstrated some of their potential by isolating and characterizing the first nitrosocarbamides complexes ( F ). , Among the unusual hydrolysis and degradation products of F is the release of nitrous oxide, which is attributed to the intermediacy of nitroxyl anions, NO – . As stable nitrosamides make up a small class of reagents, and because we sought to extend this potentially useful chemistry as a source of nitroxyl anions, we are exploring related compounds with carbamate-like character.…”

Section: Introductionmentioning

confidence: 99%

2,3,5-Metallotriazoles: Amphoteric Mesoionic Chelates from Nitrosoguanidines

et al. 2021

View full text Add to dashboard Cite

Soluble nitrosoguanidine- and N-methylnitrosoguanidine-based metallotriazole complexes of ruthenium(II) monocarbonyls have been prepared and characterized. Both nitrosoguanidines prove to be strong chelates with the formally π-accepting nitroso nitrogen binding cis to carbon monoxide and a π-donating amide trans to the CO. The resulting ensemble consists of ruthenium examples of 1-metallo-2,3,5-triazoles. The ruthenium coordination sphere is completed by anions, either H–, Cl–, or Ph–, trans to the nitroso group as well as two mutually trans PPh3 groups. The π-donating amide group is formally sp2 hybridized with a planar nitrogen to give a strongly bound five-membered chelating anion. Together, these results illustrate the remarkable potential for the nitrosoguanidinates as a family of new metal chelates.

show abstract

Involvement of Mutation-based Inhibition of β-Catenin Phosphorylation at Ser33 in the Malignant Progression of Lung (Pre)neoplastic Lesions Induced by N-nitrosobis(2-hydroxypropyl)amine in Male Fischer 344 Rats

Igarashi

Yoshida

Watanabe

et al. 2007

Lung

View full text Add to dashboard Cite

In this study we investigated the Ser33 phosphorylation status of beta-catenin protein in relation to genomic mutations in lung (pre)neoplastic lesions induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in male Fischer 344 rats. Six-week-old animals received 2000 ppm of BHP in the drinking water for 8 weeks and were sacrificed 12 weeks thereafter. Histopathologically, 69 of 75 rats demonstrated multiple lung (pre)neoplastic lesions, classified into 27 slight and 33 advanced hyperplasias (preneoplasms) and 61 neoplasms, including adenomas, adenocarcinomas, and adenosquamous carcinomas. Nucleotide mutation analysis of the beta-catenin gene detected a total of 33 mutations in 12 assessed lung (pre)neoplastic lesions. The mutations tended to accumulate in positions near the phosphorylation region of the gene, between codons 33 and 45. Immunohistochemical analysis showed beta-catenin protein expression to be increased and its localization changed from the cell membrane to the cytoplasm and finally the nuclei with advancing malignancy of the lung lesions. In contrast, the expression of phosphorlyated beta-catenin protein at Ser33 was weakened in lung (pre)neoplastic lesions compared to normal lung tissues. These results suggest that BHP-induced mutation of the beta-catenin gene results in amino acid conversions in its product protein, which in turn lead to inhibition of phosphorylation of the protein and escape from protein degradation. These phenomena might contribute to the malignant progression of the lung (pre)neoplastic lesions, which start from the relatively early stage in lung carcinogenesis.

show abstract

Molecular Aspects during Multi-step Chemical Induced Carcinogenesis in the Lung and Pancreas

Cited by 3 publications

References 44 publications

Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

2,3,5-Metallotriazoles: Amphoteric Mesoionic Chelates from Nitrosoguanidines

Involvement of Mutation-based Inhibition of β-Catenin Phosphorylation at Ser33 in the Malignant Progression of Lung (Pre)neoplastic Lesions Induced by N-nitrosobis(2-hydroxypropyl)amine in Male Fischer 344 Rats

Contact Info

Product

Resources

About