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Effect of DNA conformation on cisplatin adduct formation.

Publication ,  Journal Article
Bubley, GJ; Xu, J; Kupiec, N; Sanders, D; Foss, F; O'Brien, M; Emi, Y; Teicher, BA; Patierno, SR
Published in: Biochem Pharmacol
March 8, 1996

The anticancer drug cis-diamminedichloroplatinum(II) (cisplatin) has been shown previously to form adducts preferentially within internucleosomal or linker DNA rather than to DNA within the nucleosome. To determine whether other "open" regions of chromatin have an increased affinity for cisplatin, adduct formation within specific chromatin domains was analyzed. There was a significant increase in cisplatin-DNA adduct formation for DNA associated with the nuclear matrix (NM) compared with other chromatin domains and total unfractionated DNA. In contrast, treatment of the same cells with trans-diamminedichloroplatinum(II) (transplatin) did not result in preferential adduct formation. These findings led to the hypothesis that it might be possible to alter DNA to make it a more favorable target for cisplatin. The effect of arginine butyrate on cisplatin-DNA adduct formation was analyzed in human cancer cells. The combination of arginine butyrate and cisplatin resulted in a concentration-responsive increase in cisplatin-DNA adduct formation in PC-3 cells and an overall increase in cisplatin-DNA adduct formation in three other human cancer cell lines. The same combination also resulted in a significant increase in drug-induced cytotoxicity at a low concentration of cisplatin. These results suggest that chromatin configuration can affect cisplatin adduct formation.

Duke Scholars

Published In

Biochem Pharmacol

DOI

ISSN

0006-2952

Publication Date

March 8, 1996

Volume

51

Issue

5

Start / End Page

717 / 721

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Pharmacology & Pharmacy
  • Nucleic Acid Conformation
  • Humans
  • DNA Adducts
  • DNA
  • Cisplatin
  • Chromatin
  • Butyrates
  • Arginine
 

Citation

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Bubley, G. J., Xu, J., Kupiec, N., Sanders, D., Foss, F., O’Brien, M., … Patierno, S. R. (1996). Effect of DNA conformation on cisplatin adduct formation. Biochem Pharmacol, 51(5), 717–721. https://doi.org/10.1016/s0006-2952(95)02256-2
Bubley, G. J., J. Xu, N. Kupiec, D. Sanders, F. Foss, M. O’Brien, Y. Emi, B. A. Teicher, and S. R. Patierno. “Effect of DNA conformation on cisplatin adduct formation.Biochem Pharmacol 51, no. 5 (March 8, 1996): 717–21. https://doi.org/10.1016/s0006-2952(95)02256-2.
Bubley GJ, Xu J, Kupiec N, Sanders D, Foss F, O’Brien M, et al. Effect of DNA conformation on cisplatin adduct formation. Biochem Pharmacol. 1996 Mar 8;51(5):717–21.
Bubley, G. J., et al. “Effect of DNA conformation on cisplatin adduct formation.Biochem Pharmacol, vol. 51, no. 5, Mar. 1996, pp. 717–21. Pubmed, doi:10.1016/s0006-2952(95)02256-2.
Bubley GJ, Xu J, Kupiec N, Sanders D, Foss F, O’Brien M, Emi Y, Teicher BA, Patierno SR. Effect of DNA conformation on cisplatin adduct formation. Biochem Pharmacol. 1996 Mar 8;51(5):717–721.
Journal cover image

Published In

Biochem Pharmacol

DOI

ISSN

0006-2952

Publication Date

March 8, 1996

Volume

51

Issue

5

Start / End Page

717 / 721

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Pharmacology & Pharmacy
  • Nucleic Acid Conformation
  • Humans
  • DNA Adducts
  • DNA
  • Cisplatin
  • Chromatin
  • Butyrates
  • Arginine