Panozzo J, Akan E, Griffiths T D, Woloschak G E
Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, IL 60439-4833, USA.
Cancer Lett. 1996 Aug 2;105(2):217-23. doi: 10.1016/0304-3835(96)04285-1.
Previous work by many groups has documented induction of the human immunodeficiency virus (HIV) long terminal repeat (LTR) following exposure of cells to ultraviolet light and other DNA damaging agents. Our experiments set out to determine the relative activation or repression of the HIV-LTR in response to two classes of chemotherapeutic agents: Doxorubicin is a DNA damage-inducing agent, and 5-fluorouracil has an antimetabolic mode of action. Using HeLa cells stably transfected with a construct in which HIV-LTR drives expression of the chloramphenicol acetyl transferase reporter gene, we demonstrated an up to ten-fold induction following doxorubicin treatment at 24 h post-treatment. This induction was repressed by treatment with salicylic acid, suggesting a role for prostaglandin/cyclo-oxygenase pathways and/or NF-kappa B in the inductive response. Induction by 5-fluorouracil, in contrast, was more modest (two-fold at most) though it was consistently elevated over controls.
许多研究小组之前的工作已证明，细胞在暴露于紫外线及其他DNA损伤剂后，人类免疫缺陷病毒（HIV）的长末端重复序列（LTR）会被诱导。我们的实验旨在确定两类化疗药物对HIV-LTR的相对激活或抑制作用：阿霉素是一种诱导DNA损伤的药物，而5-氟尿嘧啶具有抗代谢作用模式。使用稳定转染了一种构建体的HeLa细胞，该构建体中HIV-LTR驱动氯霉素乙酰转移酶报告基因的表达，我们证明在阿霉素处理后24小时，诱导作用增强了多达10倍。水杨酸处理可抑制这种诱导作用，这表明前列腺素/环氧化酶途径和/或核因子κB在诱导反应中发挥作用。相比之下，5-氟尿嘧啶的诱导作用较为适度（最多两倍），但与对照组相比始终有所升高。
