Acceleration of regeneration of mucosa in small intestine damaged by ionizing radiation using anabolic steroids

• Published in: Radiation research Vol. 175; no. 3; p. 367
• Main Authors: Ishihara, Hiroshi, Tanaka, Izumi, Yakumaru, Haruko, Tanaka, Mika, Satoh, Akiko, Ishiwata, Akiko, Yokochi, Kazuko, Kurematsu, Ayako, Ueda, Jun-ichi, Shibata, Tomohiro, Hachiya, Misao, Akashi, Makoto
• Format: Journal Article
• Language: English
• Published: United States 01.03.2011
• Subjects: Anabolic Agents - pharmacology; Animals; Cell Line; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Dose-Response Relationship, Drug; Epithelial Cells - drug effects; Epithelial Cells - radiation effects; Intestinal Mucosa - cytology; Intestinal Mucosa - drug effects; Intestinal Mucosa - physiology; Intestinal Mucosa - radiation effects; Intestine, Small - cytology; Intestine, Small - diagnostic imaging; Intestine, Small - drug effects; Intestine, Small - physiology; Male; Mice; Radiography; Rats; Regeneration - drug effects; Regeneration - radiation effects; Steroids - pharmacology; Survival Rate; Time Factors
• DOI: 10.1667/rr2154.1

Damage to intestine is a serious problem after accidental radiation exposure. To examine substances to ameliorate damage by postirradiation administration, we focused on the regeneration process after irradiation of the intestine. Using experimental systems, the effects of clinically used sex hormones on regeneration were compared. An anabolic steroid, nandrolone (19-nortestosterone), stimulated proliferation in IEC-6 epithelial cells. A single injection of 19-nortestosterone ester with prolonged action into mice 24 h after abdominal irradiation at a lethal dose of 15.7 Gy showed significant life-saving effects. Regeneration indicators such as microcolonies of BrdU-incorporated cells at day 5 and c-myb mRNA expression levels at day 4 were enhanced by 19-nortestosterone administration. In contrast, high concentrations of estradiol inhibited growth of IEC-6 cells. Treatment of abdominally irradiated mice with estradiol ester decreased levels of regeneration indicators and survival. These results suggest the effectiveness of the anabolic steroid as well as the importance of manipulation of steroid receptors in the recovery of mucosa damaged by radiation.