Abstract
A major obstacle in the successful treatment of malignancies is the emergence of drug resistance. We have chosen a Chinese hamster model system to study the gene(s) responsible for multiple drug resistance and the mechanisms by which they arise. To analyze DNA rearrangements, we used adriamycin(ADR)-resistant subclones of V79 cells, 77A and LZ which are resistant to a 5-fold or 3000-fold concentration respectively of ADR relative to V79, and C5, a colchicine-resistant subline of CHO cells which is cross-resistant to a 150-fold concentration of ADR. DNA from these lines was assayed for the presence of amplified sequences by a novel in-gel renaturation technique (I.B. Roninson, Nuc. Acids Res. 11:5413, 1983). Both LZ and C5 cells contain amplified DNA fragments, a subset of which were commonly amplified in these two independently selected lines, thereby suggesting that they contain the gene(s) responsible for a common mechanism of drug-resistance. We have cloned one of the commonly amplified fragments and shown that the degree of amplification of this fragment correlated with the degree of drug resistance. We have also used this fragment as a probe to isolate several phage clones from a genomic library of LZ DNA. Transcription of these clones is being analyzed. We are currently extending these studies to include an analysis of DNA from newly diagnosed and relapsed patients with leukemia.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
