Radioprotection of 1,2-dimethylhydrazine-initiated colon cancer in rats using low-dose γ rays by modulating multidrug resistance-1, cytokeratin 20, and β-catenin expression.
Ionizing radiation is a widely used therapy for solid tumors. However, high-dose ionizing radiation causes apoptosis, transforms normal cells into tumor cells, and impairs immune functions, leading to the defects in the removal of damaged or tumor cells. In contrast, low-dose radiation has been reported to exert various beneficial effects in cells. This experimental study investigated the effect of γ rays at low dose on the development of colorectal tumor in a 1,2-dimethylhydrazine (DMH)-induced colon cancer. Colorectal tumor model was induced in Wistar rats by subcutaneous injection of DMH (20 mg/kg) once a week for 15 weeks. Starting from zero day of DMH injection, a single low dose of whole-body γ irradiation of 0.5 Gy/week was applied to the rats. A significant reduction in lipid peroxidation, nitric oxide, and elevation in the glutathione content and antioxidant enzyme activity (superoxide dismutase and catalase) were observed after γ irradiation comparing with DMH group. Moreover, γ ray reduced the expressions of multidrug resistance 1 (MDR1), β-catenin, and cytokeratin 20 (CK20) those increased in DMH-treated rats. However, survivin did not change with γ ray treatment. A histopathological examination of the DMH-injected rats revealed ulcerative colitis, dysplasia, anaplasia, and hyperchromasia. An improvement in the histopathological picture was seen in the colon of rats exposed to γ rays. In conclusion, the present results showed that low-dose γ ray significantly inhibited DMH-induced colon carcinogenesis in rats by modulating CK20, MDR1, and β-catenin expression but not survivin expression.
National Center for Radiation Research and Technology, Atomic Energy Authority (AEA), Cairo, Egypt.
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HM
Nabil
Department of Zoology and Entomology, Faculty of Science, Helwan University, Helwan, Cairo, Egypt.
B N
BN
Hassan
Department of Zoology and Entomology, Faculty of Science, Helwan University, Helwan, Cairo, Egypt.
A A
AA
Tohamy
National Center for Radiation Research and Technology, Atomic Energy Authority (AEA), Cairo, Egypt.
H F
HF
Waaer
Department of Zoology and Entomology, Faculty of Science, Helwan University, Helwan, Cairo, Egypt aest1977@hotmail.com.
A E
AE
Abdel Moneim
D019813:1,2-Dimethylhydrazine; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D002273:Carcinogens; D002374:Catalase / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D005720:Gamma Rays / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D053554:Keratin-20 / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002273:Carcinogens; D053554:Keratin-20; D051176:beta Catenin; D009569:Nitric Oxide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D019813:1,2-Dimethylhydrazine
1,2-dimethylhydrazine; Gamma ray; colon cancer; radioprotection