Intestinal tumours induced in<i>Apc<sup>Min/+</sup></i>mice by X-rays and neutrons

Ellender, M.; Harrison, J. D.; Meijne, Emmy; Huiskamp, R.; Kozlowski, R.; Haines, Jackie; Edwards, Alan; Ainsbury, Elizabeth A.; Moody, J.C.; Bouffler, Simon; Cox, Roger

doi:10.3109/09553002.2011.542542

Cited by 11 publications

(10 citation statements)

References 35 publications

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“…The Min mice develop on an average 35 to 45 adenomas and these may appear as early as 60 days after birth. Others and we have reported that exposure of APC Min/+ mice to low-LET radiation causes significant increases in intestinal tumors relative to unirradiated controls [24]–[26]. We have also shown that 4 Gy 56 Fe radiation induced greater intestinal tumorigenesis than equitoxic 5 Gy γ irradiation in these mice [25].…”

Section: Introductionsupporting

confidence: 61%

Heavy Ion Radiation Exposure Triggered Higher Intestinal Tumor Frequency and Greater β-Catenin Activation than γ Radiation in APCMin/+ Mice

et al. 2013

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Risk of colorectal cancer (CRC) after exposure to low linear energy transfer (low-LET) radiation such as γ-ray is highlighted by the studies in atom bomb survivors. On the contrary, CRC risk prediction after exposure to high-LET cosmic heavy ion radiation exposure is hindered due to scarcity of in vivo data. Therefore, intestinal tumor frequency, size, cluster, and grade were studied in APCMin/+ mice (n = 20 per group; 6 to 8 wks old; female) 100 to 110 days after exposure to 1.6 or 4 Gy of heavy ion 56Fe radiation (energy: 1000 MeV/nucleon) and results were compared to γ radiation doses of 2 or 5 Gy, which are equitoxic to 1.6 and 4 Gy 56Fe respectively. Due to relevance of lower doses to radiotherapy treatment fractions and space exploration, we followed 2 Gy γ and equitoxic 1.6 Gy 56Fe for comparative analysis of intestinal epithelial cell (IEC) proliferation, differentiation, and β-catenin signaling pathway alterations between the two radiation types using immunoblot, and immunohistochemistry. Relative to controls and γ-ray, intestinal tumor frequency and grade was significantly higher after 56Fe radiation. Additionally, tumor incidence per unit of radiation (per cGy) was also higher after 56Fe radiation relative to γ radiation. Staining for phospho-histone H3, indicative of IEC proliferation, was more and alcian blue staining, indicative of IEC differentiation, was less in 56Fe than γ irradiated samples. Activation of β-catenin was more in 56Fe-irradiated tumor-free and tumor-bearing areas of the intestinal tissues. When considered along with higher levels of cyclin D1, we infer that relative to γ radiation exposure to 56Fe radiation induced markedly reduced differentiation, and increased proliferative index in IEC resulting in increased intestinal tumors of larger size and grade due to preferentially greater activation of β-catenin and its downstream effectors.

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Section: Introductionsupporting

confidence: 61%

Heavy Ion Radiation Exposure Triggered Higher Intestinal Tumor Frequency and Greater β-Catenin Activation than γ Radiation in APCMin/+ Mice

et al. 2013

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“…Intriguingly, prior work has shown that radiation exposure increases the burden of intestinal tumor development in APC Min/+ mice in a dose-dependent manner, possibly through additional downstream effects on Wnt signaling. 15 …”

Section: Discussionmentioning

confidence: 99%

Therapy-Associated Polyposis as a Late Sequela of Cancer Treatment

Yurgelun

Hornick

Curry

et al. 2014

Clinical Gastroenterology and Hepatology

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Survivors of childhood cancers are at increased risk of developing secondary gastrointestinal cancers, including colorectal cancer later in life, possibly due to abdominopelvic radiotherapy and/or alkylating chemotherapy exposure. Profuse gastrointestinal polyposis is associated with rare, inherited colorectal cancer predisposition syndromes, most commonly caused by mutations in the Adenomatous Polyposis Coli (APC) and MutY Homolog (MYH) genes. We report five patients with gastrointestinal polyposis developing many years after radiotherapy and chemotherapy for a childhood cancer. All had normal genetic testing of the APC and MYH genes. Childhood chemotherapy and/or radiotherapy exposure may be an unrecognized cause of acquired gastrointestinal polyposis.

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“…Epidemiological observations linking radiation and colorectal cancer (CRC) are also well supported by studies in animal models43536. Apart from carcinogenesis, radiation exposure has also been reported to cause metabolic and hormonal alterations related to growth and proliferation in human as well as in animal studies373839404142434445.…”

mentioning

confidence: 92%

Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine

Suman

Kumar

Fornace

et al. 2016

Sci Rep

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Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as 56Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of 56Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of 56Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract.

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Intestinal tumours induced inApc^Min/+mice by X-rays and neutrons

Cited by 11 publications

References 35 publications

Heavy Ion Radiation Exposure Triggered Higher Intestinal Tumor Frequency and Greater β-Catenin Activation than γ Radiation in APCMin/+ Mice

Heavy Ion Radiation Exposure Triggered Higher Intestinal Tumor Frequency and Greater β-Catenin Activation than γ Radiation in APCMin/+ Mice

Therapy-Associated Polyposis as a Late Sequela of Cancer Treatment

Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine

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Intestinal tumours induced inApcMin/+mice by X-rays and neutrons

Cited by 11 publications

References 35 publications

Heavy Ion Radiation Exposure Triggered Higher Intestinal Tumor Frequency and Greater β-Catenin Activation than γ Radiation in APCMin/+ Mice

Heavy Ion Radiation Exposure Triggered Higher Intestinal Tumor Frequency and Greater β-Catenin Activation than γ Radiation in APCMin/+ Mice

Therapy-Associated Polyposis as a Late Sequela of Cancer Treatment

Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine

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Intestinal tumours induced inApc^Min/+mice by X-rays and neutrons