ISSN:
1432-0843
Keywords:
Key words DNA repair
;
Antineoplastic agents
;
alkylating
;
Drug resistance
;
neoplasm
;
Tumor cells
;
cultured
;
Medulloblastoma
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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 O 6-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 O 6-benzylguanine partially restored sensitivity to BCNU. Both cell lines were deficient in the human mismatch protein MutLα. 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).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002800050865
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