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© 1994 Oxford University Press

research-article

Transcription-independent repair of nitrogen mustard-induced N-alkylpurines in the c-myc gene in Burkitt's lymphoma CA46 cells

Karsten Wassermann, Patrick M. O'Connor 1, Joany Jackman 1, Alfred May 2 and Vilhelm A. Bohr 2

Department of Toxicology and Biology, National Institute of Occupational Health Lersø Parkallé 105, DK-2100 Copenhagen, Denmark
1Laboratory of Molecular Pharmacology, Division of Cancer Treatment, Developmental Therapeutics Program, National Cancer Institute NIH, Bethesda MD 20892, USA
2Laboratory of Molecular Genetics, National Institute of Aging NIH, Baltimore, MD 21224, USA

Recently, it has been demonstrated that N-alkylpurines produced by nitrogen mustard are excised more rapidly from actively transcribing genes compared to non-coding regions of the overall genome. Such studies have suggested that transcriptional activity is a determinant of the rate of removal of these DNA lesions. We have examined the removal of nitrogen mustard-induced N-alkylpurines in the actively transcribed/translocated and transcriptionally repressed native alleles of the c-myc gene in Burkitt's lymphoma, CA46 cells. Burkitt's lymphoma cells, exhibiting a c-myc translocation that can be distinguished from the native allele by Southern blotting, provide a useful model system in which to explore regulatory elements that govern DNA repair in transcriptionally active genes. Northern analysis verified the selective allelic expression of the translocated c-myc gene in CA46 cells. At the drug exposure examined, nitrogen mustard produced a similar level of N-alkylpurines in the two alleles of c-myc. Also, the kinetics of lesion repair from both c-myc alleles over a 24 h repair incubation period was of the same order of magnitude: ~34% and ~25% of nitrogen mustard-induced N-alkylpurines were removed by 8 h; ~72% and ~66% of nitrogen mustard lesions were removed by 24 h from the untranslocated and translocated alleles respectively. The untranslocated allele did not become transcriptionally activated upon drug treatment and nitrogen mustard produced a suppression of c-myc message levels from the translocated allele. Therefore, our results suggest that the rate of repair of nitrogen mustard-induced N-alkylpurines is independent of transcriptional activity of the c-myc gene in Burkitt's lymphoma. These findings are discussed in terms of the current views about the mechanisms of gene-specific repair.


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