THE EFFECTS OF 5-FLUOROURACIL AND DOXORUBICIN ON EXPRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LONG TERMINAL REPEAT

Previous work by many groups has documented induction of the human imm unodeficiency virus (HIV) long terminal repeat (LTR) following exposur e of cells to ultraviolet light and other DNA damaging agents. Our exp eriments set out to determine the relative activation or repression of the HIV-LTR in response to two classes of chemotherapeutic agents: Do xorubicin is a DNA damage-inducing agent, and 5-fluorouracil has an an timetabolic 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 in duction following doxorubicin treatment at 24 h post-treatment, This i nduction was repressed by treatment with salicylic acid, suggesting a role for prostaglandin/cyclo-oxygenase pathways and/or NF-kappa B in t he inductive response. Induction by 5-fluorouracil, in contrast, was m ore modest (two-fold at most) though it was consistently elevated over controls.