Abstract
BackgroundRadiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes.MethodsMouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred.ResultsGenistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group.ConclusionGenistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients.
Highlights
Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage
Apoptosis was recognized by TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining of entire apoptotic bodies
The administration of genistein decreased the average number of apoptotic cells in the crypts in 10 Gy irradiated group, there was no significant difference between the vehicleand genistein-treated groups exposed to 10 Gy irradiation (Figure 2D)
Summary
Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes. Accompanying injury to the surrounding intestinal tissue may result in serious morbidity and occasional mortality. This socalled radiation enterocolitis is a major clinical problem because it is relatively unresponsive to usual therapies and because of the intractable problems it may cause to radiation in clinical and other conditions, can be identified [4]. The antioxidant activity of genistein may protect against radiation-induced cellular damage in cancer patients. Little is known about the protective effect of genistein against radiationinduced intestinal injury
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