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5-氟尿嘧啶和5-氟脱氧尿苷单独使用以及与正常核酸前体联合使用,对选择用于强氏类黏液瘤基因低表达和高表达品系小鼠发育的影响。

The effects of 5-fluorouracil and 5-fluorodeoxyuridine used alone and in combination with normal nucleic acid precursors on development of mice in lines selected for low and high expression of Strong's luxoid gene.

作者信息

Forsthoefel P F, Williams M L

出版信息

Teratology. 1975 Feb;11(1):1-13. doi: 10.1002/tera.1420110102.

Abstract

Pregnant female mice selected for plus- and minus-modifying genes of the limb-skeleton effects of Strong's luxoid gene (1st) were injected ip on day 10 of gestation with 10 or 20 mg/kg 5-fluorouracil (5-FU) or 5-fluorodeoxyuridine (5-FUdR). The incidence and degree of expression of the effects (polydactyly, ectrodactyly, radial hemimelia, tibial hemimelia, pelvic girdle shifts, deformed caudal vertebrae) varied according to the teratogen and dose level. The addition of an equimolecular amount of thymidine, thymine, or uracil greatly potentiated the effects of 20 mg/kg 5-FU, usually resulting in death of the embryos. The addition of an equimolecular amount of thymidine but not of the embryos. The addition of an equimolecular amount of thymidine but not of thymine or uracil partly protected against the effects of 5-FUdR. Both teratogens increased the expression of ist on the limb skeleton. The interactions of the teratogens with the major gene were inhibited by minus- and promoted by plus-modifying genes of 1st. The effects of the teratogenic treatments may be mediated by cell death.

摘要

选择具有斯特朗氏类光泽基因(1型)肢体骨骼效应的正负修饰基因的怀孕雌性小鼠,在妊娠第10天腹腔注射10或20毫克/千克的5-氟尿嘧啶(5-FU)或5-氟脱氧尿苷(5-FUdR)。效应(多指畸形、缺指畸形、桡骨半肢畸形、胫骨半肢畸形、骨盆带移位、尾椎骨畸形)的发生率和表达程度因致畸剂和剂量水平而异。添加等分子数量的胸苷、胸腺嘧啶或尿嘧啶可极大地增强20毫克/千克5-FU的效应,通常导致胚胎死亡。添加等分子数量的胸苷而非胸腺嘧啶或尿嘧啶可部分预防5-FUdR的效应。两种致畸剂均增加了1型对肢体骨骼的表达。致畸剂与主基因的相互作用被1型的负修饰基因抑制,被正修饰基因促进。致畸处理的效应可能由细胞死亡介导。

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