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 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.
Panozzo
J
J
Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, IL 60439-4833, USA.
Akan
E
E
Griffiths
T D
TD
Woloschak
G E
GE
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects* / Q000528:radiation effects; D017930:Genes, Reporter / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D016325:HIV Long Terminal Repeat / Q000187:drug effects* / Q000528:radiation effects; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D014162:Transfection; D014466:Ultraviolet Rays
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D004317:Doxorubicin; D005472:Fluorouracil