Effects of DNA damaging agents on gene expression in two human cancer cell lines.
In two human cancer cell lines, the breast mcf-7 and the T-cell leukemia MOLT4, we investigated the cytotoxicity of four antineoplastic agents having different mechanisms of action. We selected doxorubicin as a DNA-topoisomerase II inhibitor, FCE24517 (a Distamycin A derivative) as a DNA minor groove binder with specificity for AT bases, melphalan as an alkylating agent and cis-platinum as an alkylating agent able to form DNA-intrastrand crosslinks. From the cytotoxicity experiments a moderately toxic (less than 10% of growth inhibition) and a highly toxic (about 75% growth inhibition) dose were selected to evaluate the expression of genes involved in cell proliferation and in cell response to extracellular insults. The expression was evaluated at early times (60 min.) and 24 hrs. after treatment. At the concentrations utilized in both cell lines we could not find any alteration in the expression of p53, gas-1 and heat shock 70. After melphalan treatment down regulation of c-myc and of the H2A histone was seen at high doses, while no significant alteration of their expression was seen with the other drugs.
Vikhanskaya
F
F
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
D'Incalci
M
M
Broggini
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D018076:DNA, Complementary; D004214:Distamycins / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016259:Genes, myc / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D008558:Melphalan / Q000494:pharmacology; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000302:isolation & purification; D012339:RNA, Ribosomal, 28S / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D000970:Antineoplastic Agents; D018076:DNA, Complementary; D004214:Distamycins; D006360:Heat-Shock Proteins; D006657:Histones; D009588:Nitrogen Mustard Compounds; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D012339:RNA, Ribosomal, 28S; D016159:Tumor Suppressor Protein p53; C066900:tallimustine; D004317:Doxorubicin; D002945:Cisplatin; D008558:Melphalan