N-ras mutation in 7,12-dimethylbenz[a]anthracene (DMBA)-induced erythroleukemia in long-evans rats

Osaka, Mariko; Matsuo, Shingo; Koh, Takashi; Liang, Ping; Kinoshita, Hidefumi; Maeda, Sakan; Sugiyama, Taketoshi

doi:10.1016/0304-3835(94)03714-t

Cited by 31 publications

(33 citation statements)

References 23 publications

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“…DMBA is a pluripotent carcinogen, which, through the formation of DNA adducts, induces initiating point mutations that alter the expression and/or activity of a number of oncogenes and tumor suppressor genes (42)(43)(44)(45). Although DMBA itself is not a known environmental carcinogen associated with ovarian cancer, it shares similar mutagenic mechanisms with other polycyclic aromatic hydrocarbons whose abundance is relatively high in air pollutants and in tobacco smoke and which have been implicated in human cancer development (46,47).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Carcinogenesis Rat Model of Ovarian Preneoplasia and Neoplasia

Stewart¹,

Querec²,

Ochman³

et al. 2004

Cancer Research

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Animal models of ovarian cancer are crucial for understanding the pathogenesis of the disease and for testing new treatment strategies. A model of ovarian carcinogenesis in the rat was modified and improved to yield ovarian preneoplastic and neoplastic lesions that pathogenetically resemble human ovarian cancer. A significantly lower dose (2 to 5 g per ovary) of 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the one ovary to maximally preserve its structural integrity. DMBA-induced mutagenesis was additionally combined with repetitive gonadotropin hormone stimulation to induce multiple cycles of active proliferation of the ovarian surface epithelium. Animals were treated in three arms of different doses of DMBA alone or followed by hormone administration. Comparison of the DMBA-treated ovaries with the contralateral control organs revealed the presence of epithelial cell origin lesions at morphologically distinct stages of preneoplasia and neoplasia. Their histopathology and path of dissemination to other organs are very similar to human ovarian cancer. Hormone cotreatment led to an increased lesion severity, indicating that gonadotropins may promote ovarian cancer progression. Point mutations in the Tp53 and Ki-Ras genes were detected that are also characteristic of human ovarian carcinomas. Additionally, an overexpression of estrogen and progesterone receptors was observed in preneoplastic and early neoplastic lesions, suggesting a role of these receptors in ovarian cancer development. These data indicate that this DMBA animal model gives rise to ovarian lesions that closely resemble human ovarian cancer and it is adequate for additional studies on the mechanisms of the disease and its clinical management.

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Section: Discussionmentioning

confidence: 99%

Characterization of a Carcinogenesis Rat Model of Ovarian Preneoplasia and Neoplasia

Stewart¹,

Querec²,

Ochman³

et al. 2004

Cancer Research

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“…DMBA is known to induce leukemia disease mixed from diffuse hepatic leukemia of erythroblastic stem cells, myelogenous leukemia, lymphoblastic leukemia, and thymic leukemia (Huggins & Sugiyama, 1966). Treatment with DMBA has been reported to produce DMBA-DNA adducts that induce a consistent type of point mutation A to T transversion at the second base in codon 61 of the N-ras gene (Osaka et al, 1995). This mutation is thought to arise from depurination of the DMBA-DNA adduct, followed by mis-replication across the unrepaired apurinic site (Schaaper, Kunkel, & Loeb, 1983;Strauss, 1985).…”

Section: Discussionmentioning

confidence: 99%

Anti-leukemic activity of a four-plant mixture in a leukemic rat model

Kabeel

Ghoneim

Mansy

2018

JoBAZ

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“…However, there was a low or no incidence of genetic alteration in the coding region of these genes (Nishiyama et al, 1995;Toyokuni et al, 1998). Here, we have taken a strategy to scan the genome of Fe-NTA-induced RCC s in F1 hybrid rats between Wistar (Shizuoka Laboratory Animal Center, Shizuoka, Japan) and Long-Evans (originally outbred from Ben May Laboratory for Cancer Research, University of Chicago, IL, USA) (Osaka et al, 1995) strains for loss of heterozygosity (LOH) with microsatellite polymorphic markers by PCR.…”

mentioning

confidence: 99%

High incidence of allelic loss on chromosome 5 and inactivation of p15INK4B and p16INK4A tumor suppressor genes in oxystress-induced renal cell carcinoma of rats

et al. 1999

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Ferric nitrilotriacetate induces oxidative damage in renal proximal tubules, a consequence of Fenton-like reaction, that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. In order to ®nd common genetic alterations in this oxystress-induced carcinogenesis model, RCCs were produced in F1 hybrid rats between Wistar and Long-Evans strains and genomes were screened for loss of heterozygosity (LOH) with microsatellite polymorphic markers by PCR. Five consecutive markers on chromosome 5 (D5Mgh5, D5Mit9, D5Mgh6, D5Mit11 and D5Mit6) showed LOH in 40% of the RCCs. As possible candidate tumor suppressor genes on chromosome 5, p15 INK4B and p16 INK4A were investigated for genetic alteration and aberrant methylation by Southern blot, PCR/SSCP/ sequencing and methylation-speci®c PCR. Genetic alteration (homozygous or hemizygous deletion with or without point mutation) or aberrant methylation were found in 30.7 and 53.8% of the RCC cases, respectively, which was proportionally associated with the histological nuclear grade and metastatic activity. Our data suggest that inactivation of p15 and p16 genes could be one of the major pathways responsible for oxystress-induced carcinogenesis.

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N-ras mutation in 7,12-dimethylbenz[a]anthracene (DMBA)-induced erythroleukemia in long-evans rats

Cited by 31 publications

References 23 publications

Characterization of a Carcinogenesis Rat Model of Ovarian Preneoplasia and Neoplasia

Characterization of a Carcinogenesis Rat Model of Ovarian Preneoplasia and Neoplasia

Anti-leukemic activity of a four-plant mixture in a leukemic rat model

High incidence of allelic loss on chromosome 5 and inactivation of p15INK4B and p16INK4A tumor suppressor genes in oxystress-induced renal cell carcinoma of rats

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