Transcriptional activation of the human immunodeficiency virus long terminal repeat sequences by cis-platin.
We constructed a recombinant plasmid, pBHIV1 carrying the long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1), linked to the chloramphenicol acetyl transferase (CAT) gene plasmid. Plasmid pBHIV1 also contains the aminoglycoside phosphotransferase gene as a selectable marker. We introduced pBHIV1 in rat 208F fibroblasts and obtained stable geneticin resistant RFBHIV1-1 transfectant cells. A further control used was plasmid p202A, which carries the mutant T24 H-ras1 promoter linked to the promotorless cat gene. Plasmid p202A also carries the aph gene as a selectable marker and was transfected into 208F cells to obtain stable transfectant RF202A-1 cells. Both RFBHIV1-1 and RF202A-1 cells expressed CAT activity from the HIV LTR and T24 H-ras1 promoters. The response to cis-platin, a platin derivative and hexadecyl-phosphocholine was studied on the HIV LTR and H-ras1 regulated CAT activity in RFBHIV1-1 and RF202A-1 cells. It was found that at 5 x 10(-5) M concentrations cis-platin stimulates by 22-fold the expression of CAT from the HIV LTR, whereas only a 4-fold stimulation was observed on the T24 H-ras1 promoter. Our results suggest caution against therapy including this compound at cytotoxic concentrations in the treatment of AIDS patients.
Spandidos
D A
DA
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Zoumpourlis
V
V
Kotsinas
A
A
Maurer
H R
HR
Patsilinacos
P
P
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002945:Cisplatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D005819:Genetic Markers; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D019868:Kanamycin Kinase; D010713:Phosphatidylcholines / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D010770:Phosphotransferases / Q000235:genetics; D010957:Plasmids; D015533:Transcriptional Activation; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects
D005029:Ethylenediamines; D005819:Genetic Markers; D010713:Phosphatidylcholines; C068760:D 17872; D010767:Phosphorylcholine; C039128:miltefosine; D015500:Chloramphenicol O-Acetyltransferase; D010770:Phosphotransferases; D019868:Kanamycin Kinase; D002945:Cisplatin