The effects of cisplatin and methotrexate on the expression of human immunodeficiency virus type 1 long terminal repeat
Abstract Previous work by many groups has documented the induction of HIV-LTR (human immunodeficiency virus-long terminal repeat) following exposure of cells or whole animals to ultraviolet (UV) light and other DNA damaging agents. In these experiments we set out to determine whether exposure to the cancer chemotherapeutic agents methotrexate and cisplatin had any effect on the expression of the HIV-LTR. Using HeLa cells stably transfected with a construct in which HIV-LTR drives the expression of the reporter gene chloramphenicol acetyl transferase (CAT), we demonstrated induction of HIV-LTR 24–48 h following exposure to 50 μM cisplatin. When UV exposure (10 Jm −2 ) was coupled with cisplatin (50 μM) treatment (which also causes DNA damage), HIV-LTR induction was additive relative to either treatment alone. Methotrexate, which depletes the medium of tetrahydrofolate and does not induce DNA damage, induced HIV-LTR at later (6–7 days) time points than cisplatin or UV treatments. When methotrexate (128 μM) and UV (10 Jm −2 ) treatments were combined, the agents were synergistic with regard to HIV induction. For both drugs, though, induction was not due to generalized transcriptional activation since both cisplatin and methotrexate induced a repression of total transcription as measured in nuclear run-on assays.
원문보기 무료다운로드 유료다운로드
- 무료 원문 정보가 존재하지 않습니다.
유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.
NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.