Genistein treatment protects mice from ionizing radiation injury

被引:117
作者
Landauer, MR [1 ]
Srinivasan, V [1 ]
Seed, TM [1 ]
机构
[1] AFRRI, Radiat Casualty Managment Team, Bethesda, MD 20889 USA
关键词
radioprotection; gamma radiation; ionizing radiation; genistein; locomotor activity; grip strength; behavior; acute toxicity;
D O I
10.1002/jat.904
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The radioprotective and behavioral effects of an acute administration of the isoflavone genistein (4,5,7-trihydroxyflavone) were investigated in adult CD2F1 male mice. Mice were administered a single subcutaneous (s.c.) dose of genistein either 24 It or 1 It before a lethal dose of gamma radiation (9.5-Gy of cobalt-60 at 0.6 Gy min(-1)). Mice received saline, PEG-400 vehicle or genistein at 3.125, 6.25, 12.5, 25, 50, 100, 200, or 400 mg kg(-1) body weight. For mice treated 24 It before irradiation there was a significant increase in 30-day survival for animals receiving genistein doses of 25 to 400 mg kg(-1) (p < 0.001). In contrast, the 30-day survival rates of mice treated with genistein I h before irradiation were not significantly different from those of the vehicle control group. Additionally, the acute toxicity of genistein was evaluated in non-irradiated male mice administered a single s.c. injection of saline, vehicle, or genistein at 100, 200 or 400 mg kg(-1). At these genistein doses there were no adverse effects, compared with controls, on locomotor activity, grip strength, motor coordination, body weight, testes weight, or histopathology. These results demonstrate that a single s.c. administration of the flavonoid genistein at non-toxic doses provides protection against acute radiation injury. Published in 2003 by John Wiley Sons, Ltd.
引用
收藏
页码:379 / 385
页数:7
相关论文
共 40 条
[1]   Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro:: Possible involvement of inhibition of survival signal transduction pathways [J].
Akimoto, T ;
Nonaka, T ;
Ishikawa, H ;
Sakurai, H ;
Saitoh, J ;
Takahashi, T ;
Mitsuhashi, N .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2001, 50 (01) :195-201
[2]   A phase II trial of subcutaneous Amifostine and radiation therapy in patients with head and neck cancer [J].
Anné, PR ;
Curran, WJ .
SEMINARS IN RADIATION ONCOLOGY, 2002, 12 (01) :18-19
[3]   STUDIES ON DIFFERENTIATION INDUCING SUBSTANCES OF ANIMAL-CELLS .1. DIFFERENOL-A, A DIFFERENTIATION INDUCING SUBSTANCE AGAINST MOUSE LEUKEMIA-CELLS [J].
ASAHI, K ;
ONO, I ;
KUSAKABE, H ;
NAKAMURA, G ;
ISONO, K .
JOURNAL OF ANTIBIOTICS, 1981, 34 (07) :919-920
[4]   HEMATOPOIETIC RADIOPROTECTION BY CREMOPHOR EL - A POLYETHOXYLATED CASTOR-OIL [J].
BERTONCELLO, I ;
KRIEGLER, AB ;
WOODCOCK, DM ;
WILLIAMS, B ;
BARBER, L ;
NILSSON, SK .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1995, 67 (01) :57-64
[5]   In vivo administration of genistein has no effect on small intestinal epithelial proliferation and apoptosis, but a modest effect on clonogen survival [J].
Booth, C ;
Hargreaves, DF ;
O'Shea, JA ;
Potten, CS .
CANCER LETTERS, 1999, 144 (02) :169-175
[6]  
Bump E.A., 1998, RADIOPROTECTORS CHEM
[7]  
Chan WH, 2000, J CELL BIOCHEM, V78, P73, DOI 10.1002/(SICI)1097-4644(20000701)78:1<73::AID-JCB7>3.0.CO
[8]  
2-P
[9]  
Cockerham L. G., 2001, PRINCIPLES METHODS T, P699
[10]   Sex steroid receptor regulation by genistein in the prepubertal rat uterus [J].
Cotroneo, MS ;
Wang, J ;
Eltoum, IEA ;
Lamartiniere, CA .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2001, 173 (1-2) :135-145