Experimental radiotherapy is currently exploring the use of the radioprotective drug WR-2721 (s-2(3-aminopropylamino) ethylphosphorothioic acid) to differentially protect normal tissue while eradicating malignant tissue. The subject of chemical radiation protection of the fetus has been virtually ignored for almost 20 years and certainly since the development of the more potent and less toxic radioprotectant WR-2721. We intend to explore the suitability of using WR-2721 as a protectant for the developing rat fetus. The rat is most susceptible to x-ray teratogenesis during the period of early organogenesis. Defects typically affect the head resulting in craniofacial abnormalities e.g., shape, shortening of the mandible and maxilla, cleft lip, palate, and face with defects of eye and ear development. Gross malformations of the CNS e.g., exencephaly or microcephaly and skeletal defects such as disorganization or absence of the ossification centers of the vertebrae, ribs, and limbs also commonly occur with radiation during this period. The most important question is whether fetal death, growth retardation and malformation induced by irradiation during the period of major organogenesis (day 9, 11 and 14 pc) can be reduced or prevented by pretreatment with WR- 2721. In order to carry out this objective we intend to determine if and when, during the period of major organogenesis, WR-1065 injected as WR-2721 can pass the placental barrier to reach the fetus (liquid scintillation and HPLC techniques). IN addition, we will assess the potential toxicity of WR-2721 to the pregnant rat and determine a suitable dose for the fetus i.e., one that will not result in death, growth retardation of malformation. Thus we will compare the effects of x-irradiation with or without WR-2721 on days 9, 11 and 14 pc at x-ray doses of 25-400 r in order to determine radiation protection factor. Preliminary data indicates that radioprotection was afforded by WR-2721. If WR-2721 would provide protection, even by a factor of 2, at x- ray doses as low as 25 r it would provide encouraging presumptive evidence for protectability at the low dose levels of less than 10 r where carcinogenesis and congenital defects are a current concern.
| Lamperti, A; Ziskin, M C; Bergey, E et al. (1990) Transdermal absorption of radioprotectors in the rat using permeation-enhancing vehicles. Radiat Res 124:194-200 |
| Sodicoff, M; Lamperti, A; Ziskin, M C (1990) Transdermal absorption of radioprotectors using permeation-enhancing vehicles. Radiat Res 121:212-9 |
