Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
The effects of 5-fluorouracil and doxorubicin on expression of human immunodeficiency virus type 1 long terminal repeat.
Cancer Lett. 1996 Aug 2;105(2):217-23. Unique Identifier : AIDSLINE MED/96319712 Panozzo J; Akan E; Griffiths TD; Woloschak GE; Center for Mechanistic Biology and Biotechnology, Argonne; National Laboratory, IL 60439-4833, USA.
Abstract:
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.
Keywords: Antibiotics, Anthracycline/*PHARMACOLOGY Antimetabolites, Antineoplastic/*PHARMACOLOGY Dose-Response Relationship, Drug Doxorubicin/*PHARMACOLOGY Fluorouracil/*PHARMACOLOGY Gene Expression Regulation, Viral/*DRUG EFFECTS/RADIATION EFFECTS Genes, Reporter/DRUG EFFECTS/GENETICS/RADIATION EFFECTS Hela Cells Human HIV Long Terminal Repeat/*DRUG EFFECTS/RADIATION EFFECTS HIV-1/GENETICS Support, U.S. Gov't, Non-P.H.S. Transfection Ultraviolet Rays JOURNAL ARTICLE 961130
M96B1847
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