The effects of vinblastine on the expression of human immunodeficiency virus type 1 long terminal repeat.
Previous work by our group has demonstrated induction of the HIV-LTR following exposure of cells to various DNA-damaging agents such as ultraviolet (UV) light, cisplatin, and doxorubicin. The current experiments were designed to determine the relative effects of the anti-mitotic drug vinblastine on expression of the HIV-LTR. Using human cervical carcinoma (HeLa) cells stably transfected with the chloramphenicol acetyl transferase (CAT) reporter transcriptionally driven by the HIV-LTR promoter, we demonstrated a 9-10-fold induction at 48-72 h following vinblastine treatment. Previous experiments had demonstrated repression of cisplatin or doxorubicin-mediated HIV induction by treatment with salicylic acid. The vinblastine induction also was repressed by salicylic acid treatment, but not by treatment with indomethacin, suggesting a role for the NF{kappa}B pathway in the inductive response. When UV exposure was coupled to the vinblastine treatment, there was no additive or synergistic effect evident, suggesting similar paths of induction between the two agents. Northern blots demonstrated that these agents were operating at the level of transcription and that salicylic acid inhibited vinblastine-mediated induction of HIV-LTR-CAT mRNA only if administered at the same time as vinblastine; addition of salicylic acid 2 h later had no effect on transcript accumulation. All combinations of treatments with vinblastine and/or salicylic acid markedly reduced cell survival.
- Research Organization:
- Argonne National Laboratory (ANL)
- Sponsoring Organization:
- ER
- DOE Contract Number:
- AC02-06CH11357
- OSTI ID:
- 937853
- Report Number(s):
- ANL/CMB/JA-22043
- Journal Information:
- Cancer Res., Journal Name: Cancer Res. Journal Issue: 5 ; May 1997 Vol. 21; ISSN 0008-5472; ISSN CNREA8
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
The effects of 5-fluorouracil and doxorubicin on expression of human immunodeficiency virus type 1 long terminal repeat
HIV transcription is induced with cell killing
Effects of gamma rays, ultraviolet radiation, sunlight, microwaves and electromagnetic fields on gene expression mediated by human immunodeficiency virus promoter
Technical Report
·
Thu Feb 29 23:00:00 EST 1996
·
OSTI ID:207377
HIV transcription is induced with cell killing
Technical Report
·
Fri Dec 31 23:00:00 EST 1993
·
OSTI ID:10114046
Effects of gamma rays, ultraviolet radiation, sunlight, microwaves and electromagnetic fields on gene expression mediated by human immunodeficiency virus promoter
Journal Article
·
Sat Oct 01 00:00:00 EDT 1994
· Radiation Research
·
OSTI ID:79336