Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1985 Feb 15;226(1):175–182. doi: 10.1042/bj2260175

Intracellular DNA damage produced by a series of diacridines.

I A Roos, L P Wakelin, S J Henry
PMCID: PMC1144690  PMID: 3977863

Abstract

The intracellular DNA damage produced by a series of diacridines after a 2 h pulse treatment of L1210 cells in culture was investigated by using the alkaline-elution technique. Like other intercalating agents, diacridines produce single-strand breaks and protein-DNA links. There is a large increase in both types of damage as the alkane chain linking the two 9-aminoacridine residues is increased beyond five methylene groups, which is consistent with the previously observed change from monofunctional to bifunctional intercalation [Wakelin, Romanos, Chen, Glaubiger, Canellakis & Waring (1978) Biochemistry 17, 5057-5063]. For linker chains of less than six methylene groups these agents produce less DNA damage than does the parent 9-aminoacridine at the same drug concentration. Unlike the monofunctional intercalators previously investigated [Ross, Glaubiger & Kohn (1979) Biochim. Biophys. Acta 562, 41-50; Zwelling, Michaels, Erickson, Ungerleider, Nichols & Kohn (1981) Biochemistry 20, 6553-6563; Zwelling, Kerrigan & Michaels (1982) Cancer Res. 42, 2687-2691; Zwelling, Michaels, Kerrigan, Pommier & Kohn (1982) Biochem. Pharmacol. 31, 3261-3267], there is no correlation between the number of single-strand breaks and protein-DNA links produced by these diacridines.

Full text

PDF
175

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cain B. F., Baguley B. C., Denny W. A. Potenial antitumor agents. 28. Deoxyribonucleic acid polyintercalating agents. J Med Chem. 1978 Jul;21(7):658–668. doi: 10.1021/jm00205a013. [DOI] [PubMed] [Google Scholar]
  2. Canellakis E. S., Bellantone R. A. Diacridines: bifunctional intercalators. II. The biological effects of putrescine, sperimidine and spermine diacridines on HeLa cells and on the L-1210 and P-388 leukemia cells. Biochim Biophys Acta. 1976 Feb 5;418(3):290–299. doi: 10.1016/0005-2787(76)90291-4. [DOI] [PubMed] [Google Scholar]
  3. Canellakis E. S., Bono V., Bellantone R. A., Krakow J. S., Fico R. M., Schulz R. A. Diacridines: bifunctional intercalators. III. Definition of the general site of action. Biochim Biophys Acta. 1976 Feb 5;418(3):300–314. doi: 10.1016/0005-2787(76)90292-6. [DOI] [PubMed] [Google Scholar]
  4. Canellakis E. S., Fico R. M., Sarris A. H., Shaw Y. H. Diacridines - double intercalators as chemotherapeutic agents. Biochem Pharmacol. 1976 Jan 15;25(2):231–236. doi: 10.1016/0006-2952(76)90304-x. [DOI] [PubMed] [Google Scholar]
  5. Canellakis E. S., Shaw Y. H., Hanners W. E., Schwartz R. A. Diacridines: bifunctional intercalators. I. Chemistry, physical chemistry and growth inhibitory properties. Biochim Biophys Acta. 1976 Feb 5;418(3):277–289. doi: 10.1016/0005-2787(76)90290-2. [DOI] [PubMed] [Google Scholar]
  6. Chen T. K., Fico R., Canellakis E. S. Diacridines, bifunctional intercalators. Chemistry and antitumor activity. J Med Chem. 1978 Sep;21(9):868–874. doi: 10.1021/jm00207a006. [DOI] [PubMed] [Google Scholar]
  7. Crothers D. M. Calculation of binding isotherms for heterogenous polymers. Biopolymers. 1968 Apr;6(4):575–584. doi: 10.1002/bip.1968.360060411. [DOI] [PubMed] [Google Scholar]
  8. Huang C. H., Mong S., Crooke S. T. Interactions of a new antitumor antibiotic BBM-928A with deoxyribonucleic acid. Bifunctional intercalative binding studied by fluorometry and viscometry. Biochemistry. 1980 Nov 25;19(24):5537–5542. doi: 10.1021/bi00565a012. [DOI] [PubMed] [Google Scholar]
  9. Kohn K. W., Ewig R. A. DNA-protein crosslinking by trans-platinum(II)diamminedichloride in mammalian cells, a new method of analysis. Biochim Biophys Acta. 1979 Mar 28;562(1):32–40. doi: 10.1016/0005-2787(79)90123-0. [DOI] [PubMed] [Google Scholar]
  10. Laurent G., Erickson L. C., Sharkey N. A., Kohn K. W. DNA cross-linking and cytotoxicity induced by cis-diamminedichloroplatinum(II) in human normal and tumor cell lines. Cancer Res. 1981 Sep;41(9 Pt 1):3347–3351. [PubMed] [Google Scholar]
  11. Le Pecq J. B., Le Bret M., Barbet J., Roques B. DNA polyintercalating drugs: DNA binding of diacridine derivatives. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2915–2919. doi: 10.1073/pnas.72.8.2915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lee J. S., Waring M. J. Bifunctional intercalation and sequence specificity in the binding of quinomycin and triostin antibiotics to deoxyribonucleic acid. Biochem J. 1978 Jul 1;173(1):115–128. doi: 10.1042/bj1730115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nelson E. M., Tewey K. M., Liu L. F. Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1361–1365. doi: 10.1073/pnas.81.5.1361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ohkuma H., Sakai F., Nishiyama Y., Ohbayashi M., Imanishi H., Konishi M., Miyaki T., Koshiyama H., Kawaguchi H. BBM-928, a new antitumor antibiotic complex. I. Production, isolation, characterization and antitumor activity. J Antibiot (Tokyo) 1980 Oct;33(10):1087–1097. doi: 10.7164/antibiotics.33.1087. [DOI] [PubMed] [Google Scholar]
  15. Pelaprat D., Delbarre A., Le Guen I., Roques B. P., Le Pecq J. B. DNA intercalating compounds as potential antitumor agents. 2. Preparation and properties of 7H-pyridocarbazole dimers. J Med Chem. 1980 Dec;23(12):1336–1343. doi: 10.1021/jm00186a010. [DOI] [PubMed] [Google Scholar]
  16. Ross W. E., Glaubiger D. L., Kohn K. W. Protein-associated DNA breaks in cells treated with adriamycin or ellipticine. Biochim Biophys Acta. 1978 Jun 22;519(1):23–30. doi: 10.1016/0005-2787(78)90059-x. [DOI] [PubMed] [Google Scholar]
  17. Ross W. E., Glaubiger D., Kohn K. W. Qualitative and quantitative aspects of intercalator-induced DNA strand breaks. Biochim Biophys Acta. 1979 Mar 28;562(1):41–50. doi: 10.1016/0005-2787(79)90124-2. [DOI] [PubMed] [Google Scholar]
  18. Wakelin L. P., Creasy T. S., Waring M. J. Equilibrium constants for the binding of an homologous series of monofunctional and bifunctional intercalating diacridines to calf thymus DNA. FEBS Lett. 1979 Aug 15;104(2):261–265. doi: 10.1016/0014-5793(79)80828-5. [DOI] [PubMed] [Google Scholar]
  19. Wakelin L. P., Romanos M., Chen T. K., Glaubiger D., Canellakis E. S., Waring M. J. Structural limitations on the bifunctional intercalation of diacridines into DNA. Biochemistry. 1978 Nov 14;17(23):5057–5063. doi: 10.1021/bi00616a031. [DOI] [PubMed] [Google Scholar]
  20. Wakelin S. P., Waring M. J. The binding of echinomycin to deoxyribonucleic acid. Biochem J. 1976 Sep 1;157(3):721–740. doi: 10.1042/bj1570721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Waring M. J., Wakelin L. P. Echinomycin: a bifunctional intercalating antibiotic. Nature. 1974 Dec 20;252(5485):653–657. doi: 10.1038/252653a0. [DOI] [PubMed] [Google Scholar]
  22. Zwelling L. A., Kerrigan D., Michaels S. Cytotoxicity and DNA strand breaks by 5-iminodaunorubicin in mouse leukemia L1210 cells: comparison with adriamycin and 4'-(9-acridinylamino)methanesulfon-m-anisidide. Cancer Res. 1982 Jul;42(7):2687–2691. [PubMed] [Google Scholar]
  23. Zwelling L. A., Michaels S., Erickson L. C., Ungerleider R. S., Nichols M., Kohn K. W. Protein-associated deoxyribonucleic acid strand breaks in L1210 cells treated with the deoxyribonucleic acid intercalating agents 4'-(9-acridinylamino) methanesulfon-m-anisidide and adriamycin. Biochemistry. 1981 Nov 10;20(23):6553–6563. doi: 10.1021/bi00526a006. [DOI] [PubMed] [Google Scholar]
  24. Zwelling L. A., Michaels S., Kerrigan D., Pommier Y., Kohn K. W. Protein-associated deoxyribonucleic acid strand breaks produced in mouse leukemia L1210 cells by ellipticine and 2-methyl-9-hydroxyellipticinium. Biochem Pharmacol. 1982 Oct 15;31(20):3261–3267. doi: 10.1016/0006-2952(82)90560-3. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES