Fine Structure of Pancreatic Adenocarcinoma Induced In Rats by 7,12-Dimethylbenz[
            a
            ]anthracene
            2

Bockman, Dale E.; Black, Owen; Mills, Luther R.; Mainz, David L.; Webster, Peter

doi:10.1093/jnci/57.4.931

Cited by 31 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A procedure for inducing cancer that resembles human pancreatic ductal adenocarcinoma has been well established (Bockman et al, 1976;Dissin et al, 1975;Rivera et al, 1997). It involves the implantation of a carcinogen, dimethylbenzanthracene (DMBA), into the pancreas of rats.…”

mentioning

confidence: 99%

“…Ductal adenocarcinoma develops in a significant proportion of the recipients over a period of months. Earlier reports were based on observations from specimens harvested several months after implantation (Bockman et al, 1976;Dissin et al, 1975;Rivera et al, 1997). A more recent study included tissue taken as soon as 2 weeks after implantation (Jimenez et al, 1999).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Origin and Development of the Precursor Lesions in Experimental Pancreatic Cancer in Rats

Bockman

Guo

Büchler

et al. 2003

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:Notwithstanding the importance of understanding how pancreatic ductal adenocarcinoma develops, the process remains controversial. A key question is whether the cells of origin of the tubular complexes that constitute precursor lesions are derived from a single cell type or from multiple types. Suggestions that they arise solely from centroacinar cells or ductal cells have been based on inference due to their morphologic appearance in tissue from patients or investigation of limited numbers of tubular complexes in animal models later in the carcinogenic process. The present study establishes clearly that two steps are involved; rapid transdifferentiation to produce tubular complexes followed later by transformation of the component cells. Animals were killed at intervals beginning 1 day after implantation of the carcinogen dimethylbenzanthracene. Transdifferentiation of acinar cells to ductal cells does not require cell division. Transition of lobules to tubular complexes begins by 2 days after implantation of carcinogen. Within 4 days after implantation well-developed tubular complexes are present. Islets participate in the process. Ductal adenocarcinoma is observed by 1 month after implantation of carcinogen. Chymotrypsin and cytokeratin localized by immunocytochemistry indicate acinar and ductal cell characteristics. Acino-ductal transdifferentiation persists in carcinogen-implanted animals, but not in controls implanted with sodium chloride crystals or subjected to sham implantation. The precursor lesions (tubular complexes) are formed by the transdifferentiation of acinar cells and to a lesser extent islet cells, with the incorporation of the duct cells pre-existing in the lobules. Therefore, cells that at one time were acinar cells, islet cells, and duct cells, provide the precursor cells for the ductal adenocarcinoma that develops from tubular complexes. The results raise the question whether the transdifferentiated cells in the tubular complexes of patients with chronic pancreatitis are more susceptible to carcinogenic influences, resulting in the increased rate of pancreatic cancer. (Lab Invest 2003, 83:853-859).

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Origin and Development of the Precursor Lesions in Experimental Pancreatic Cancer in Rats

Bockman

Guo

Büchler

et al. 2003

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…The ultrastructural observations are consistent with the view (83) that this may be effected by a process of selective autophagy of rough ER and zymogen, the cellular end product of which has the fine structural morphology of a centroacinar or ductular cell. Although a similar loss of differentiation has been shown to result from nontumorigenic insults (85)(86)(87), it is significant that acinar cell dedifferentiation is also a characteristic feature of pancreatic carcinogenesis in both the rat (50) and the guinea pig (57,58).…”

Section: Changes In Acinar Cellsmentioning

confidence: 95%

“…DMBA in addition induced ductal atypia and hyperplasia; however acinar and "ductular" hyperplasia were also present in a few animals. Furthermore, Bockman and his co-workers (50), in an electron microscope study of DMBA-induced adenocarcinomas, observed the presence within them of cells with distinctive acinar cell characters, casting considerable doubt upon their ductal origin. Subsequently, Bockman and his colleagues (51)(52)(53) found that epithelial tubular complexes which develop at early stages of tumor induction in this model, and which might be interpreted on the basis of their histology as ductal or ductular proliferation, contain cells of intermediate character between acinar and ductal types.…”

Section: Ratmentioning

confidence: 99%

Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence.

Flaks¹

1984

Environ Health Perspect

View full text Add to dashboard Cite

Pancreatic carcinogenesis in the Syrian hamster, induced by 3-oxidized derivatives of N-nitroso-di-npropylamine, constitutes a valuable model of human cancer of the exocrine pancreas. In both species the majority of tumors are adenocarcinomas: superficially, on the basis of their histological appearance, these appear to be ductal in origin. However, sequential analysis, by electron microscopy, of the development of pancreatic neoplasia in the hamster model indicates that acinar cells may participate in the histogenesis of "ductal" adenomas and carcinomas. Acinar cells appear to undergo changes in differentiation, including pseudoductular transformation, giving rise to a new population of cells that resemble ductular or centroacinar types. This new population may then proliferate to form, first, cystic foci and subsequently cystadenomas and adenocarcinomas. Mucous metaplasia appears to develop at late stages of tumor development. Although the participation of ductular and centroacinar cells in pancreatic carcinogenesis cannot be excluded, very few tumors arise from the ductal epithelium.It is possible that some human pancreatic adenocarcinomas may also have their origin from dysplastic acinar cells, by analogy with the hamster model: focal acinar dysplasia being common in human pancreatic cancer patients.

show abstract

“…Chemical agents (N-nitroso-bis(2-oxopropyl) amine and 7,12-dimethylbenzanthracene) and transgenic mice (PDX-1-Cre;LSL-KRAS G12D and P48 +/Cre ;LSL-KRAS G12D ) are the pancreatic carcinogenesis models more used. Pancreatic implantation of 7,12-dimethylbenzanthracene (DMBA) have previously been reported [10][11][12][13][14][15] and produces a phenotype of ductal adenocarcinoma with mutated K-ras 11;16 . Zehnder et al first described the induction of PDA in mice using DMBA, reducing the time of neoplasia induction to only 2 months 14 .…”

Section: Introductionmentioning

confidence: 99%

Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice: effects of alcohol and caffeine

et al. 2007

View full text Add to dashboard Cite

Purpose:To evaluate the effects of alcohol and caffeine in a pancreatic carcinogenesis mouse model induced by 7,12-dimethylbenzantracene (DMBA), according to the PanIN classification system. Methods: 120 male, Mus musculus, CF-1 mice were divided into four groups. Animals received either water or caffeine or alcohol or alcohol + caffeine in their drinking water. In all animals, 1 mg of DMBA was implanted into the head of the pancreas. After 30 days, euthanasia was performed; excised pancreata were then fixed in formalin, stained with hematoxylin-eosin and categorized as follows: normal ducts, reactive hyperplasia, PanIN-1A, PanIN-1B, PanIN-2, PanIN-3 or adenocarcinoma. Results: PanIN lesions were verified in all groups. Adenocarcinoma was detected in 15% of animals in the caffeine group, 16.6% in the water group, 23.8% in the alcohol + caffeine group and 52.9% in the alcohol group (P<0.05). Conclusions: The experimental pancreatic carcinogenesis mouse model using DMBA effectively induces PanIN lesions and pancreatic adenocarcinoma. This study verified the association between alcohol use and pancreatic adenocarcinoma; caffeine did not present the same effect Key words: Caffeine. 9,10-Dimethyl-1,2-benzanthracene. Adenocarcinoma. Pancreas. Mice. RESUMOObjetivo: Avaliar os efeitos do álcool e da cafeína na carcinogênese pancreática induzida pelo 7,12-dimetilbenzantraceno (DMBA) em camundongos, descrevendo as lesões de acordo com a classificação das neoplasias pacreáticas intraepiteliais (PanIN). Métodos: 120 camundogos machos, Mus musculus, CF-1 foram divididos em quatro grupos. Animais receberam água ou cafeína ou álcool ou álcool + cafeína para beber. Em todos animais, 1 mg de DMBA foi implantado na cabeça do pâncreas. Após 30 dias, eutanásia foi realizada, o pâncreas foi removido, fixado em formalina e corado com hematoxilina e eosina sendo classificado em: ductos normais, hiperplasia reativa, PanIN-1A, PanIN-1B, PanIN-2, PanIN-3 ou adenocarcinoma. Resultados: Neoplasias pancreáticas intraepiteliais foram encontradas em todos grupos. Adenocarcinoma foi detectado em 15% dos animais do grupo cafeína, 16,6% do grupo água, 23,8% do grupo álcool + cafeína e 52,9% do grupo álcool (P<0,05). Conclusões: O modelo experimental de carcinogênese pancreática em camundongos utilizando DMBA induz neoplasias pancreáticas intraepiteliais (PanIN) e adenocarcinoma pancreático. Este estudoverificou associação entre álcool e adenocarcinoma pancreático, enquanto a cafeína não demonstrou este efeito. Descritores: Cafeína. 9,10-Dimetil-1,2-benzantraceno. Adenocarcinoma. Pâncreas. Camundongos. -ORIGINAL ARTICLE Acta Cirúrgica Brasileira -Vol 22 (3) 2007 -203Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice: effects of alcohol and caffeine

show abstract

Fine Structure of Pancreatic Adenocarcinoma Induced In Rats by 7,12-Dimethylbenz[ a ]anthracene 2

Cited by 31 publications

References 0 publications

Origin and Development of the Precursor Lesions in Experimental Pancreatic Cancer in Rats

Origin and Development of the Precursor Lesions in Experimental Pancreatic Cancer in Rats

Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence.

Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice: effects of alcohol and caffeine

Contact Info

Product

Resources

About