Amundson S A, Do K T, Fornace A J
National Institutes of Health, National Cancer Institute, Division of Basic Science, Bethesda, Maryland 20892, USA.
Radiat Res. 1999 Sep;152(3):225-31.
Using cells of a human myeloid tumor cell line (ML-1), we have detected induction of several stress-responsive genes by doses of gamma rays below 50 cGy. We found a linear dose-response relationship for induction of CDKN1A (formerly known as CIP1/WAF1) and GADD45 mRNA levels over the range of 2-50 cGy, with no evidence of a threshold for induction. Although exposures to 2 and 5 cGy did not result in any detectable reduction in cloning efficiency or increased apoptosis in ML-1 cells, these exposures did produce a transient delay of cells in the phases of the cell cycle in addition to the observed up-regulation of CDKN1A and GADD45. The relative induction of genes such as CDKN1A by radiation doses that produce little toxicity indicates that surviving cells do contribute significantly to the observed stress responses. These studies should provide insight into the molecular responses to physiologically relevant doses that cannot necessarily be extrapolated from high-dose studies.
利用人类髓系肿瘤细胞系（ML-1）的细胞，我们检测到低于50 cGy的γ射线剂量可诱导多种应激反应基因。我们发现，在2 - 50 cGy范围内，CDKN1A（以前称为CIP1/WAF1）和GADD45 mRNA水平的诱导呈线性剂量反应关系，没有诱导阈值的证据。虽然暴露于2 cGy和5 cGy不会导致ML-1细胞的克隆效率有任何可检测到的降低或凋亡增加，但这些暴露除了观察到CDKN1A和GADD45上调外，还确实使细胞周期各阶段出现短暂延迟。产生低毒性的辐射剂量对CDKN1A等基因的相对诱导表明，存活细胞确实对观察到的应激反应有显著贡献。这些研究应能深入了解对生理相关剂量的分子反应，而这些反应不一定能从高剂量研究中推断出来。
