Total cellular ribose nucleic acid analysis of multi-drug resistant cancer cells.

OBJECTIVE The present study is designed to elucidate the correlation between gene dosage and increased messenger ribose nucleic acid (RNA) level in multi-drug resistant cancer cells. METHODS The human lymphoblasts CCRF-CEM (CEM) and CEM-vinblastine (VBL) 10, CEM-VBL 20, CEM-VBL 40, CEM-VBL 60, cell line CEM-VBL 80, and CEM-VBL 100 were derived from CEM VBL 10 by single step selection technique. For the analysis of total RNA and deoxyribonucleic acid (DNA), both Northern-Southern blot analysis were carried out on all sensitive and resistant cell lines. Part of the study was conducted at the Immunology Laboratory, Higher Institute of Health, Rome and the other part was conducted at the Middle Euphrates Center for Cancer Researches, Kufa University, Iraq, between 1990 and 2000. RESULTS Total cellular RNA was analyzed to quantitate the levels of expression of multi-drug resistant-one gene with extent of its amplification in CEM-sensitive and resistant cell lines. Only the CEM-VBL resistant over expresion the multi-drug resistant-one gene but in CEM-sensitive cells do not. The over-expresses appears to correlate proportionally with the level of drug resistance. No such correlation has been detected with regard to the genomic DNA. CONCLUSION It appears that the first step in the transition from drug sensitive to drug resistant is increasing levels of messenger RNA followed by gene amplification. Furthermore, once the gene is amplified, it remains at the same level of amplification regardless of the concentration of drug in which given cells have been selected.