Skalko R G, Packard D S, Caniano D A, Sax R D
Teratology. 1975 Oct;12(2):157-64. doi: 10.1002/tera.1420120208.
Pregnant female ICR mice were administered, ip, either a trace (200 muCi/kg) or teratogenic (200 muCi + 300 mg/kg) dose of [6(-3)H] 5-iododeoxyuridine (IdU) on day 10 of gestation. Maternal liver, spleen, intestine, and kidneys, and placentas and embryos were removed at various time intervals after injection, weighed, and homogenized in cold 0.5 m perchloric acid. The half-lives of IdU-derived nucleotides in the acid-soluble fraction ranged from 31-46 min (trace) to 57-131 min (teratogenic) for the tissues analyzed. [3H]IdU was incorporated into the DNA of all mitotically active tissues after both dosages. The presence of the label in iodouracil was demonstrated by thin-layer chromatography of DNA bases extracted from maternal spleen and embryo. Growth of embryos following injection on day 10 resulted in decreased 3H-specific activity in the DNA fraction and concomitant retention of total activity. It is suggested that the previously demonstrated embryotoxicity of IdU is related to its retention at its presumed intracellular site of action.
在妊娠第10天,给怀孕的雌性ICR小鼠腹腔注射微量(200微居里/千克)或致畸剂量(200微居里 + 300毫克/千克)的[6(-3)H]5-碘脱氧尿苷(IdU)。在注射后的不同时间间隔,取出母鼠的肝脏、脾脏、肠道和肾脏,以及胎盘和胚胎,称重后在冰冷的0.5 M高氯酸中匀浆。对于所分析的组织,酸溶性部分中IdU衍生核苷酸的半衰期范围为31 - 46分钟(微量)至57 - 131分钟(致畸剂量)。两种剂量下,[3H]IdU均被掺入所有有丝分裂活跃组织的DNA中。通过对从母鼠脾脏和胚胎中提取的DNA碱基进行薄层色谱分析,证实了碘尿嘧啶中标记的存在。在第10天注射后胚胎的生长导致DNA部分中3H比活性降低,同时总活性得以保留。提示先前证明的IdU胚胎毒性与其在假定的细胞内作用位点的滞留有关。