Preneoplastic and Neoplastic Progression during Hepatocarcinogenesis in Mice Injected with Diethylnitrosamine in Infancy

Goldfarb, Stanley; Pugh, Thomas D.; Koen, Hirofumi; He, Yingkun

doi:10.2307/3429545

Cited by 12 publications

(15 citation statements)

References 11 publications

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“…The occurrence, growth and evolution of DEN-induced mouse hepatic proliferative and neoplastic lesions depends on several factors including the dose scheme and administration route of DEN and also age, strain and gender of mice (1,2). Our finding of hepatocellular adenomas in 10-months-old C56BL/6 male mice that were treated with 5 mg/kg BW of DEN matches the results of other published studies using mice of comparable genetic backgrounds and the same gender and similar experimental designs (6,29).…”

Section: Discussionsupporting

confidence: 81%

“…Among them, the chemically induced model that utilizes diethylnitrosamine (DEN) for HCC initiation is widely used and well-characterized. This model recapitulates aspects of liver injury and fibrosis and hepatitis, which both are the basis of human HCC (1,2,4,6). For that, and because it is comparable to its human counterpart in terms of cancer-associated gene expression patterns and carcinogenetic pathways, it is considered among the best-fit experimental models of HCC (5).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Wnt‑1 blockade in DEN‑induced hepatocellular adenomas of mice

et al. 2017

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Abstract. Recent evidence has suggested that downregulation of the Wnt/β-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt-1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days. At that time, DEN-treated mice had multiple variably-sized hepatic cell adenomas. Anti-Wnt-1 was particularly potent in suppressing the expression of critical elements of the Wnt/β-catenin signaling pathway, such as β-catenin and Frizzled-1 receptor, however, not Dickkopf-related protein 1. This effect co-existed with the suppression of Cyclin D1, FOXM1, NF-κΒ and c-Jun commensurate with proliferation and apoptosis blockade in hepatocellular adenomas, and reduced Bcl-2 and c-Met in the serum of mice. Nonetheless, tumor size and multiplicity were found to be unaffected, suggesting that apoptosis may be equally important to proliferation in the context of counteracting DEN induced hepatocellular adenomas of mice.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Effects of Wnt‑1 blockade in DEN‑induced hepatocellular adenomas of mice

et al. 2017

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“…However, the quantitative difference in UG promotion activity between male and female mice most likely is, in part, a consequence of the 16-week time point chosen for analysis. AHF in the DEN/control group were about fourfold larger in male than in female mice at this time point (11), which is consistent with the well-established faster growth of AHF in male mice in the infant mouse model (28,29). Thus, it would have been relatively difficult to demonstrate the same fourfold increase in size of AHF in male versus female mice at the 16-week time point.…”

Section: Discussionsupporting

confidence: 50%

“…UG did not increase nonlesioned hepatocyte LI in initiation control or DEN-initiated mice (Table 3). The hepatocyte LI of AHF was substantially greater than that of nonlesioned liver, as expected (27)(28)(29). The mean hepatocyte LI of AHF from DEN/UG-treated mice was 29% greater (p < 0.01) than the mean hepatocyte LI of AHF from mice treated with DEN alone (Table 3).…”

mentioning

confidence: 62%

Promotion of Hepatic Preneoplastic Lesions in Male B6C3F 1 Mice by Unleaded Gasoline

Standeven¹,

Wolf²,

Goldsworthy³

1995

Environmental Health Perspectives

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“…In CDF1 mice, the sensitivity of females to the induction of liver tumor was approximately twice that of males . Because it is well known that oval cell proliferation and basophilic foci are induced by hepatocarcinogens (Goldfarb et al, 1983;He et al, 1994), female rasH2 mice are considered to be more sensitive to hepatocarcinogenesis induced by IQ than male rasH2 mice, as in the case of CDF1 mice. IQ is metabolized by cytochrome P450 (CYP) 1A2 mainly in the liver and induces its activating enzyme (Nerurkar et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

A 26-Week Carcinogenicity Study of 2-Amino-3-Methylimidazo[4,5-f]Quinoline in rasH2 Mice

et al. 2006

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To evaluate the carcinogenic susceptibility of rasH2 mice to 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ), 7-week-old rasH2 mice and their wild-type littermates (non-Tg mice) of both the sexes were fed a diet containing 0 or 300 ppm IQ for 26 weeks. Microscopical examinations revealed that the proliferative lesions of the forestomach, including squamous cell hyperplasias, papillomas, and carcinomas, were frequently encountered in male and female rasH2 mice fed with IQ. In non-Tg mice, no significant differences in the incidence of forestomach lesions were observed between the 0 ppm and 300 ppm groups. Histopathological changes such as periportal hepatocellular hypertrophy and oval cell proliferation in the liver were more apparent in female rasH2 and non-Tg mice than in males, and the incidence of hepatocellular altered foci significantly increased in female rasH2 mice in the 300 ppm group as compared to that in the 0 ppm group. These results suggest that the carcinogenic potential of IQ can be detected in rasH2 mice by a 26-week, short-term carcinogenicity test.

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Preneoplastic and Neoplastic Progression during Hepatocarcinogenesis in Mice Injected with Diethylnitrosamine in Infancy

Cited by 12 publications

References 11 publications

Effects of Wnt‑1 blockade in DEN‑induced hepatocellular adenomas of mice

Effects of Wnt‑1 blockade in DEN‑induced hepatocellular adenomas of mice

Promotion of Hepatic Preneoplastic Lesions in Male B6C3F 1 Mice by Unleaded Gasoline

A 26-Week Carcinogenicity Study of 2-Amino-3-Methylimidazo[4,5-f]Quinoline in rasH2 Mice

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