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.
Similar content being viewed by others
References
Bostock, C.J., Christie, S.: Quinacrine fluorescence staining of chromosomes and its relationship to DNA base composition. Exp. Cell Res. 86, 157–161 (1974)
Calendi, E., Marco, A.D., Reggiani, M., Scarpinato, B., Valentini, L.: On physico-chemical interactions between daunomycin and nucleic acids. Biochim. biophys. Acta (Amst.) 103, 25–49 (1965)
Caspersson, T., Farber, S., Foley, G.E., Kudynowski, J., Modest, E.J., Simonsson, E., Wagh, U., Zeck, L.: Chemical Differentiation along metaphase chromosomes. Exp. Cell Res. 49, 219–222 (1968)
Chan, L.M., McCarter, J.A.: The interaction of aminoacridines with DNA. Biochim. biophys. Acta (Amst.) 204, 252–254 (1970)
Comings, D.E.: The structure and function of chromatin. In advance in human genetics Vol. 3, chapter 5 (H. Harris and K. Hirschhorn, eds.), pp. 237–394. NewYork-London: Plenum Press 1972
Comings, D.E., Drets, M.E.: Mechanisms of chromosome banding IX. Are variations in DNA base composition adequate to account for quinacrine, Hoechst 33258 and daunomycin banding? Chromosoma (Berl.) 56, 199–211 (1976)
Comings, D.E., Kovacs, B.W., Avelino, E., Harris, D.C.: Mechanism of chromosome banding V. Quinacrine banding. Chromosoma (Berl.) 50, 111–145 (1975)
Dev, V.G., Grewal, M.S., Miller, D.A., Kouri, R.E., Hutton J.J., Miller, O.J.: The quinacrine fluorescence karyotype of Mus musculus and demonstration of strain differences in secondary constriction. Cytogenetics 10, 436–451 (1971)
Dev, V.G., Warburton, D., Miller, O.J., Miller, D.A., Erlanger, B.F., Beiser, S.M.: Consistent pattern of binding of anti-adenosine antibodies to human metaphase chromosomes. Exp. Cell Res. 74, 288–293 (1972)
Ehrlich, S.D., Thiery, S.P., Devillers-Theiry, A., Giorgio Bernardi: A new approach to the study of nucleotide sequences in DNA's. Nucleic Acid Res. 1, 87–96 (1974)
Ellison, J.R., Barr, H.J.: Quinacrine fluorescence of specific chromosome regions: late replication and high A:T content in Samoaia lionensis. Chromosoma (Berl.) 36, 375–390 (1972)
Felsenfeld, G., Hirschman, S.Z.: A neighbor-interaction analysis of the hypochromism and spectra of DNA. J. molec Biol. 13, 407–427 (1965)
Hilwig, I., Gropp, I.: Staining of constitutive heterochromatin in mammalian chromosomes with a new fluorochrome. Exp. Cell Res. 75, 122–126 (1972)
Jacobson, A., Firtel, R.A., Lodish, H.F.: Transcription of polydeoxythymidylate sequences in the genome of the cellular slime mold, Dictyostelium discoideum. Proc. nat. Acad. Sci. (Wash.) 71, 1607–1611 (1974)
Johnston, F.P., Sande, J.H. van de, Lin, C.C.: Anthracyclines as chromosome banding agents. Canad. J. Genet. Cytol. 18, 565 (1976)
Kersten, W., Kersten, H., Szybalski, W.: Physicochemical properties of complexes between deoxyribonucleic acid and antibiotics and antibiotics which affect ribonucleic synthesis. Biochemistry 5, 236–244 (1966)
Latt, S.A., Wohlleb, J.C.: Optional studies on the interaction of 33258 Hoechst with DNA, chromatin, and metaphase chromosomes. Chromosoma (Berl.) 52, 297–316 (1975)
Lieberman, M.W.: Fractionation of mouse DNA in preparative Ag±Cs2SO4 gradients. Biochim. biophys. Acta (Amst.) 324, 309–319 (1973)
Lin, C.C., Sande, J.H. van de: Differential fluorescent staining of human chromosomes with daunomycin and adriamycin — the D-bands. Science 190, 61–63 (1975)
Lin, C.C., Sande, J.H. van de, Smink, W.K., Newton, D.R.: Quinacrine fluorescence and Q-banding patterns of human chromosomes. Canad. J. Genet. Cytol. 17, 81–92 (1975)
Lin, C.C., Uchida, I.A.: Fluorescent banding of chromosomes (Q-bands). In: Methods and applications of tissue culture (P.F. Kruse and M.K. Patterson, eds.), pp. 778–781. New York: Academic Press 1973
Mazin, A.L.: Evolution of DNA structure: Direction, mechanism, rate.: J. molec Evol. 8, 211–249 (1976)
Modest, E.J., Sengupta, S.K.: Chemical correlates of chromosome banding. In chromosome identifiation. Proc. 23rd Nobel Symposium 1972 (T. Caspersson and L. Zech, eds.), pp. 327–334. New York-London: Academic Press 1973
Mol, J.N.M., Flavell, R.A., Borst, P.: The Presence of (dA·dT) 20–25 Tracts in the DNA of Primitive Eukaryotes. Nucleic Acid Res. 3, 2367–2377 (1976)
Morgan, A.R., Pulleyblank, D.E.: Native and denatured DNA, cross-linked and palindromic DNA and circular covalently-closed DNA analyzed by a sensitive fluorometric procedure. Biochem. biophys. Res. Commun. 61, 346–353 (1974)
Morgan, A.R., Wells, R.D., Khorana, H.B.: Studies on polynucleotides LXXIV. Direct translation in vitro of single-stranded DNA-like polymers with repeating nucleotide sequences in the presence of neomycin B. J. molec. Biol. 26, 477–497 (1967)
Olson, K., Luk, D., Harvey, C.L.: Formation of poly-dA·poly-dT by E. coli DNA polymerase in the presence of anthracycline antibiotics. Biochim. biophys. Acta (Amst.) 277, 269 (1972)
Pachmann, U., Rigler, R.: Quantum yield of acridine interacting with DNA of defined base sequence. Exp. Cell Res. 72, 602–608 (1972)
Rowley, J.D., Bodmer, W.F.: Relationship of centromeric heterochromatin to fluorescent banding patterns of metaphase chromosomes in mouse. Nature (Lond.) 231, 503–506 (1971)
Russell, G.J., Walker, P.M.B., Elton, R.A., Subak-Sharpe, J.H.: Doublet frequency analysis of fractionated vertebrate nuclear DNA. J. molec. Biol. 108, 123 (1976)
Sande, J.H. van de, Lin, C.C., Jorgenson, K.F.: Reverse banding on chromosomes produced by a guanosine-cytosine specific DNA binding antibiotic: Olivomycin. Science 195, 400–402 (1977)
Schreck, R.R., Erlanger, B.F., Miller, O.J.: The use of antinucleoside antibodies to probe the organization of chromosomes denatured by ultra-violet irradiation. Exp. Cell Res. 88, 31–39 (1974)
Schweizer, D.: Reverse fluorescent chromosome banding with chromomycin and DAPI. Chromosoma (Berl.) 58, 307–324 (1976)
Shenkin, A., Burdon, R.H.: Deoxyadenylate-rich and deoxyguanylate-rich regions in mammalian DNA. J. molec. Biol. 85, 19–39 (1974)
Shugalin, A.V., Frank-Kamenetstii, N.D., Lazurkin, Yu.S.: Viscometric investigation of block heterogeneity of DNA. Molec. Biol. 4, 221–227 (1970)
Simola, K., Selander, R.K., Chapelle, A. de la, Corneo, G., Ginelli, E.: Molecular basis of chromosome banding. I. Effect of mouse DNA fractions on two fluorescent dyes in vitro. Chromosoma (Berl.) 51, 199–205 (1975)
Strauss, N.A., Birnboim, H.C.: Poly pyrimidine sequences found in eukaryotic DNA have been conserved during evolution. Biochim. biophys. Acta (Amst.) 454, 419–428 (1976)
Subak-Sharpe, J.H.: The doublet pattern of the nucleic acid in relation to the origin of viruses. In: Handbook of molecular cytology (J. Lima-de-Faria, ed.). Amsterdam: North-Holland 1969
Tubbs, R.K., Ditmars, W.E., Winkle, Q.V.: Heterogeneity of the interaction of DNA with acriflavine. J. molec. Biol. 9, 545–557 (1964)
Waring, M.J.: Variation of the supercoils in closed circular DNA by binding of antibiotics and drugs: evidence for molecular models involving intercalation. J. molec. Biol. 54, 247–279 (1970)
Weisblum, B.: Why centric regions of quinacrine-treated mouse chromosomes show diminished fluorescence. Nature (Lond.) 246, 150–151 (1973)
Weisblum, B., Haseth, P.L. de: Quinacrine, a chromosome stain specific for deoxyadenylate-rich regions in DNA. Proc. nat. Acad. Sci. (Wash.) 69, 629–632 (1972)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Johnston, F.P., Jorgenson, K.F., Lin, C.C. et al. Interaction of anthracyclines with DNA and chromosomes. Chromosoma 68, 115–129 (1978). https://doi.org/10.1007/BF00287144
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00287144