摘要
本文对致癌剂二乙基亚硝胺(DEN)和促癌剂巴豆油对大鼠肝α_1-抑制因子3(α_1- I_s)基因表达的影响进行了观察。结果表明:在腹腔注射DEN(200mg/kg·b.w.)后2h,α_1- I_3 RNA水平即显著下降;4h左右有所回升,约为正常水平的四分之一;然后又下降至极低水平,并一直保持该水平至24h。同时,c-myc RNA在2h则被诱导,约为正常水平的2-3倍;之后,即在4至24h内虽有波动,但基本处于正常水平。在腹腔注射巴豆油(18mg/kg.b.w.)后1h,α_1-I_3RNA水平即下降,约为正常水平的1/8,此后有所回升,约为正常水平的1/3-1/4;在同样条件下,ODC和C-fos RNA能被巴豆油诱导而增加。我们以前的工作表明,在大多数(75％,12/16)由DEN所诱发的大鼠肝癌中,α_1- I_3RNA水平显著下降,且基因结构发生了变化。综合这些结果,说明α_1- I_3基因或与该基因表达有关的蛋白调控因子可能是致癌剂DEN或促癌剂TPA的作用靶分子。该基因表达异常的意义及机理正在深入研究中。
The effects of carcinogen DEN and tumor promtor croton oil (as a source of TPA) on the expression of rat liver ********a1-inhibitor 3 gene were investigated using Slot blot analysis method.Results indicated that very low levels of ********a1-I3 RNA as compared with normal were detected at 2h, restored but only about 1/4 of the control levels at 4h, and then the very low level of **********a1-I3 transcripts persisted till 24h after a single dose administration of DEA (200mg/kg, b.w.).Cocurrently, c-myc RNA was increased at 2h and fell down towards normal levels from 4 to 24 h after DEN treatment.Croton oil which induced the expression of hepatic ODC and c-fos gene negatively regulated the expression of *********a1-I3 gene.There was a marked decrease (about 7-to 8-fold) in the level of ***********a1-I3 RNA at 1h, following a single dose injection of croton oil (18mg/kg,b.w.), and returned and persisted towards approximately 1/4 of normal levels from 3 to 7 h.Our previous studies have revealed that in most primary rat hepatomas (75%, 12/16) induced by DEN, the levels of ***********a1-I3 RNA were significantly diminished or undetectable, furthermore, the structure of *************a1-I3 gene in these hepatomas has been changed, for instance, hrpermethylation and RFLP.Taken together, these findings suggest that *************a1-I3 gene and/or the trans-acting elements controlling the expression of **************a1-I3 gene are the targets for the attarck of carcinogen DEN and tumor promoter TPA.Further Studies are required to determine the significance and mechanisms of the altered expression of ********a1-I3 gene during carci-aogenesis.
基金
国家自然科学基金
