Loss of heterozygosity in spontaneous and x-ray-induced intestinal tumors arising in F1 hybridMin mice: Evidence for sequential loss ofApc+ andDpc4 in tumor development

Haines, Jackie; Dunford, Rosemary; Moody, J.C.; Ellender, M.; Cox, Roger; Silver, Andrew

doi:10.1002/1098-2264(200008)28:4<387::aid-gcc4>3.0.co;2-h

Cited by 27 publications

(17 citation statements)

References 52 publications

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“…Our observations are in agreement with data previously published from X-irradiated ApcMin mice (Okamoto and Yonekawa 2005; Haines et al 2000; Ellender et al 2006). We also sought to assess in vivo how exposure to high-linear energy transfer (LET) radiation, such as 1 GeV/n 56 Fe ions, may affect intestinal tumorigenesis compared to low-LET radiation, like γ rays.…”

Section: Discussionsupporting

confidence: 94%

Enhanced intestinal tumor multiplicity and grade in vivo after HZE exposure: mouse models for space radiation risk estimates

Trani

Datta

Doiron

et al. 2010

Radiat Environ Biophys

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Carcinogenesis induced by space radiation is considered a major risk factor in manned interplanetary and other extended missions. The models presently used to estimate the risk for cancer induction following deep space radiation exposure are based on data from A-bomb survivor cohorts and do not account for important biological differences existing between high-linear energy transfer (LET) and low-LET-induced DNA damage. High-energy and charge (HZE) radiation, the main component of galactic cosmic rays (CGR), causes highly complex DNA damage compared to low-LET radiation, which may lead to increased frequency of chromosomal rearrangements, and contribute to carcinogenic risk in astronauts. Gastrointestinal (GI) tumors are frequent in the United States, and colorectal cancer (CRC) is the third most common cancer accounting for 10% of all cancer deaths. On the basis of the aforementioned epidemiological observations and the frequency of spontaneous precancerous GI lesions in the general population, even a modest increase in incidence by space radiation exposure could have a significant effect on health risk estimates for future manned space flights. Ground-based research is necessary to reduce the uncertainties associated with projected cancer risk estimates and to gain insights into molecular mechanisms involved in space radiation-induced carcinogenesis. We investigated in vivo differential effects of γ-rays and HZE ions on intestinal tumorigenesis using two different murine models, ApcMin/+ and Apc1638 N/+. We showed that γ- and/or HZE exposure significantly enhances development and progression of intestinal tumors in a mutant-line-specific manner, and identified suitable models for in vivo studies of space radiation–induced intestinal tumorigenesis.

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Section: Discussionsupporting

confidence: 94%

Enhanced intestinal tumor multiplicity and grade in vivo after HZE exposure: mouse models for space radiation risk estimates

Trani

Datta

Doiron

et al. 2010

Radiat Environ Biophys

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“…Female CBA/H mice were mated with C57BL/6 Min/ϩ male mice and the F 1 progeny genotyped to identify CHB6 Min/ϩ hybrid mice (6,7).…”

Section: Methodsmentioning

confidence: 99%

“…The Apc Min mutation predisposes mice to the spontaneous development of small intestinal tumors and is the mouse genetic homologue of human familial adenomatous polyposis (2,3). The heterozygous deficiency of Apc also predisposes to radiation-induced tumorigenesis (4)(5)(6). X-ray-induced tumors were found to be predominantly adenomas.…”

Section: Introductionmentioning

confidence: 99%

Direct Single Gene Mutational Events Account for Radiation-Induced Intestinal Adenoma Yields inApc^Min/+Mice

Ellender¹,

Harrison²,

Edwards³

et al. 2005

Radiation Research

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Data on the induction of small intestinal tumors, predominantly adenomas, by X radiation in Apc(Min/+) mice are reported. Comparison of these incidences with estimates of radiation-induced direct single gene mutation frequencies taken from the literature support the hypothesis that direct mutational loss of Apc+ is the sole requirement for initiation of adenoma. Furthermore, estimates of radiation-induced initiation of adenoma per target stem cell in this animal model are similar to or less than radiation-induced direct somatic gene mutation frequencies. Therefore, while the data reported here do not preclude a role for genomic instability in tumor progression, it is not necessary in this model to postulate the involvement of radiation-induced transmissible genomic instability in initiation of intestinal adenoma.

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“…A homozygous mutant state has not been described in humans for these genes and is assumed to be embryonic lethal; mice homozygous (-/-) often show embryonic lethality, while heterozygous (+/-) mice develop tumors showing LOH as they age. This phenomenon has been found for induced mouse mutants of p53 [48][49][50] , Menl 51 , Pten [52][53][54][55] , apc 46,56 , Tsc2…”

Section: Loss Of Heterozygosity (Loh) In Mouse and Human Mutantsmentioning

confidence: 67%

Preneoplastic and Precancerous Lesions in Rodents: Morphologic and Molecular Characteristics.

Ward

2002

J Toxicol Pathol

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Cancer evolves through a sequential process from normal cells in many tissues of humans and animals. The natural history of tumor development can be seen histologically and by biochemical and molecular changes. There are two common basic pathways for the formation of malignant epithelial tumors; through preneoplastic foci and benign tumors (carcinoma developing in an adenoma) in parenchymal tissue or progression from intraepithelial neoplasia (IN) (atypical hyperplasia, noninvasive carcinoma, carcinoma in situ), a lesion in flat or lining epithelium. In epithelial-lining tissues of humans and rodents (e.g. cervix, mammary gland, prostate, skin), these lesions have been described as IN. In solid epithelial organs (liver, kidney, endocrine tissues) focal hyperplasia leads to adenomas. Adenomas develop foci of carcinoma, a process that is more common in rodents than in humans. These precancerous lesions in many rodent tissues often have multiple biochemical and molecular lesions which can be similar or different from those found in malignant tumors. The rodent molecular lesions include mutations in oncogenes (K-ras, H-ras) and tumor suppressor genes (p53, β-catenin,apc) or loss of heterozygosity (LOH) in tumor suppressor genes of mutant mouse models. This manuscript will review specific sequential morphologic and molecular lesions in the histopathogenesis of cancer in several rodent tissues. The significance of molecular lesions for diagnosis of rodent lesions will be discussed. (J Toxicol Pathol 2002; 15: 123-128)

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Loss of heterozygosity in spontaneous and x-ray-induced intestinal tumors arising in F1 hybridMin mice: Evidence for sequential loss ofApc+ andDpc4 in tumor development

Cited by 27 publications

References 52 publications

Enhanced intestinal tumor multiplicity and grade in vivo after HZE exposure: mouse models for space radiation risk estimates

Enhanced intestinal tumor multiplicity and grade in vivo after HZE exposure: mouse models for space radiation risk estimates

Direct Single Gene Mutational Events Account for Radiation-Induced Intestinal Adenoma Yields inApc^Min/+Mice

Preneoplastic and Precancerous Lesions in Rodents: Morphologic and Molecular Characteristics.

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Loss of heterozygosity in spontaneous and x-ray-induced intestinal tumors arising in F1 hybridMin mice: Evidence for sequential loss ofApc+ andDpc4 in tumor development

Cited by 27 publications

References 52 publications

Enhanced intestinal tumor multiplicity and grade in vivo after HZE exposure: mouse models for space radiation risk estimates

Enhanced intestinal tumor multiplicity and grade in vivo after HZE exposure: mouse models for space radiation risk estimates

Direct Single Gene Mutational Events Account for Radiation-Induced Intestinal Adenoma Yields inApcMin/+Mice

Preneoplastic and Precancerous Lesions in Rodents: Morphologic and Molecular Characteristics.

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Direct Single Gene Mutational Events Account for Radiation-Induced Intestinal Adenoma Yields inApc^Min/+Mice