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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A092
Earlier, we have described the process of active dissociation or "DNA
clearing" from noncovalently bound agents in living mammalian cells. The
vital fluorescent bisbenzimidazole dye Hoechst-33342, which binds tightly
but not covalently to DNA in the minor groove, was used for studying
interactions of noncovalently binding agents with DNA. Multiple drug
resistance (MDR) in tumor cells is related to the expression of transport
proteins that alter cellular drug transport and distribution. To obtain new
lines characterized by enhanced process of active dissociation of noncovalently
bound agent from DNA or DNA clearing, we selected human and rodent cell
lines that are hyperresistant to the Hoechst 33342. The cell lines selected
from Chinese hamster cell line AA8 were named AA8Hoe-R-1 - AA8Hoe-R10, and
the cell lines selected from mouse L cells were called LHoe-R-1 - LHoe-R-10,
cell lines selected from human cell line Mg63 were named Mg63 Hoe-R-1 - Mg63
Hoe-R-10. All mutants were analyzed with flow cytometric technique and half
of them were characterized by an enchanced dissociation of the
bisbenzimidazole dye - DNA complex. As we believe, the enchanced level of
DNA clearing was caused by the amplification of some genes because the
gradual increase of Hoechst resistance in the same cell line resulted from
the increase in the ability to remove the dye from DNA. These lines were
shown to be also resistant to netropsin and mitomycin C. We concluded that
we obtained a new group of MDR cell lines characterized by an enhanced
capacity of DNA clearing.
A NEW GROUP OF MAMMALIAN MDR CELL LINES WITH ENHANCED CAPACITY OF µDNA
CLEARING FROM NONCOVALENTLY BOUND AGENTS
Levina VV, Varfolomeeva EY, Sukhareva EB, Drobchenko EA,
Filatov MV
Petersburg Nuclear Physics Institute, Gatchina, St.Petersburg,
Russia