Abstract
It was determined that some common DNA sequences had been amplified in all the lines, but that the total DNA region amplified varied among lines. We compared the DM-containing AMD-resistant line to a line with homogeneously staining regions (HSR), which had been derived from it by prolonged maintenance under constant selection in AMD. With 1 probe it was found that some previously unamplified DNA sequences were amplified in the HSR-carrying line, suggesting a complex mechanism behind the transition from DM to HSR. In contrast, identical Southern blot patterns were found in the AMD-resistant line with DM and 4 subclones with different HSR, indicating that in this case the HSR arose by integration of an amplicon present in the DM (without extensive rearrangement) rather than by a second amplification event. The tentative conclusion from our experiments is that in SEWA cells MDR is accomplished by the amplification of DNA sequences. The primary amplified DNA resides in DM, which under constant selection tend to be replaced by HSR. This second step may or may not be accompanied by amplification of previously unamplified DNA sequences.
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