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Multiple DNA repair mechanisms and alkylator resistance in the human medulloblastoma cell line D-283 Med (4-HCR).

Publication ,  Journal Article
Dong, Q; Johnson, SP; Colvin, OM; Bullock, N; Kilborn, C; Runyon, G; Sullivan, DM; Easton, J; Bigner, DD; Nahta, R; Marks, J; Modrich, P; Friedman, HS
Published in: Cancer Chemother Pharmacol
1999

PURPOSE: We have previously reported preferential repair of DNA interstrand crosslinks in the 4-hydroperoxycyclophosphamide-resistant human medulloblastoma cell line D-283 Med (4-HCR). We now report further studies that explored the potential mechanisms underlying this repair. METHODS: Limiting dilution assays and Western, Southern, and Northern blots were used to compare specific differences between D-283 Med (4-HCR) and its parental line D-283 Med. RESULTS: D-283 Med (4-HCR) was cross-resistant to melphalan and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), with O6-alkylguanine-DNA alkyltransferase (AGT) levels of 466+/-164 fmol/mg protein; AGT levels in the parental line, D-283 Med, were 76+/-96 fmol/mg. The increase in AGT activity was not a result of gene amplification. Depleting AGT with O6-benzylguanine partially restored sensitivity to BCNU. Both cell lines were deficient in the human mismatch protein MutLalpha. ERCC4 mRNA and poly(ADP-ribose) polymerase levels were similar in both cell lines, and ERCC1 mRNA levels were 2- to 2.5-fold lower in D-283 Med (4-HCR). Topoisomerase I levels were 2- to 2.5-fold higher in D-283 Med compared with D-283 Med (4-HCR). CONCLUSION: These results, while illustrating the multiple differences between D-283 Med and D-283 Med (4-HCR), do not explain the enhanced DNA interstrand crosslink repair seen in D-283 Med (4-HCR).

Duke Scholars

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1999

Volume

43

Issue

1

Start / End Page

73 / 79

Location

Germany

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Protein Biosynthesis
  • Poly(ADP-ribose) Polymerases
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Medulloblastoma
  • Indicator Dilution Techniques
  • Humans
  • Endonucleases
 

Citation

APA
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MLA
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Dong, Q., Johnson, S. P., Colvin, O. M., Bullock, N., Kilborn, C., Runyon, G., … Friedman, H. S. (1999). Multiple DNA repair mechanisms and alkylator resistance in the human medulloblastoma cell line D-283 Med (4-HCR). Cancer Chemother Pharmacol, 43(1), 73–79. https://doi.org/10.1007/s002800050865
Dong, Q., S. P. Johnson, O. M. Colvin, N. Bullock, C. Kilborn, G. Runyon, D. M. Sullivan, et al. “Multiple DNA repair mechanisms and alkylator resistance in the human medulloblastoma cell line D-283 Med (4-HCR).Cancer Chemother Pharmacol 43, no. 1 (1999): 73–79. https://doi.org/10.1007/s002800050865.
Dong Q, Johnson SP, Colvin OM, Bullock N, Kilborn C, Runyon G, et al. Multiple DNA repair mechanisms and alkylator resistance in the human medulloblastoma cell line D-283 Med (4-HCR). Cancer Chemother Pharmacol. 1999;43(1):73–9.
Dong, Q., et al. “Multiple DNA repair mechanisms and alkylator resistance in the human medulloblastoma cell line D-283 Med (4-HCR).Cancer Chemother Pharmacol, vol. 43, no. 1, 1999, pp. 73–79. Pubmed, doi:10.1007/s002800050865.
Dong Q, Johnson SP, Colvin OM, Bullock N, Kilborn C, Runyon G, Sullivan DM, Easton J, Bigner DD, Nahta R, Marks J, Modrich P, Friedman HS. Multiple DNA repair mechanisms and alkylator resistance in the human medulloblastoma cell line D-283 Med (4-HCR). Cancer Chemother Pharmacol. 1999;43(1):73–79.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1999

Volume

43

Issue

1

Start / End Page

73 / 79

Location

Germany

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Protein Biosynthesis
  • Poly(ADP-ribose) Polymerases
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Medulloblastoma
  • Indicator Dilution Techniques
  • Humans
  • Endonucleases