Interaction of anthracyclines with DNA and chromosomes

Abstract

Daunomycin and adriamycin were previously found to produce Q-like banding patterns on chromosomes. The interaction of several anthracyclines with both natural and synthetic DNAs and chromosomes has been investigated in more detail. Daunomycin fluorescence is almost completely quenched by natural DNAs with varying base composition from 31 to 72% G-C and by the alternating polymer poly-d(G-C)·poly-d(G-C). In contrast, daunomycin fluorescence is quenched by only 50% when the dye interacts with synthetic A-T polymers. Thus, differential quenching of daunomycin fluorescence can account for the production of bright bands at contiguous A-T sequences along the chromosome. Slight differences in fluorescence quenching between the repeating and homopolymeric A-T duplex DNAs were observed which can be attributed to differences in affinity of daunomycin for these DNAs. The aminosugar moiety of daunomycin, daunosamine, increases the binding of daunomycin to DNA and also enhances chromosome banding. — Nogalamycin, which displays no differential quenching with the different DNAs in solution, also fails to produce bands on chromosomes. — These findings suggest that non-random nucleotide sequence arrangements along the chromosome are a basic determinant for dye interaction to produce the observed banding patterns. Specific banding procedures may determine the accessibility of these sites within the chromosomal DNA.