SALICYLIC-ACID INHIBITS ULTRAVIOLET-INDUCED AND CIS-PLATINUM-INDUCED HUMAN-IMMUNODEFICIENCY-VIRUS EXPRESSION

Previous studies have shown that exposure of HeLa cells stably transfe cted with an HIV-long terminal repeat-chloramphenicol acetyltransferas e (HIV-LTR-CAT) construct to many DNA-damaging agents (such as UV ligh t) induces expression from the HIV LTR. By culturing the cells with sa licylic acid we demonstrated dose-dependent repression of this UV- cis -platinum (cis-Pt)-induced HIV expression. While salicylic acid treatm ent, indomethacin treatment, UV exposure, or cis-Pt treatment alone de creased viability by up to 50%, equal numbers of viable cells were use d for the CAT assays. Repression was evident if salicylic acid was adm inistered 2 h before, at the same time as, or up to 6 h after exposure to the DNA-damaging agent. The kinetics were similar for UV- and for cis-Pt-induced HIV expression, and induction was dependent on the UV d ose or cis-Pt concentration added to the culture. pH changes of the me dia alone in the absence of salicylic acid did not affect HIV expressi on. Indomethacin (100 mu M) did not affect UV- or cis-Pt-induced HIV e xpression. These results suggest a role for the prostaglandins or the cyclooxygenase pathway or both in HIV induction mediated by DNA-damagi ng agents.