| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Pathology, Duke University, Durham, North Carolina 27710 [S.M.B.] and Department of Environmental Sciences and Engineering, School of Public Health [J. E. C., T.R.C., J.A.S., T.R.S.] and Department of Pathology [J.A.S., T.R.S.], The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
We examined the toxicity, mutagenicity, and mutational spectra of N-ethyl-N-nitrosourea (ENU) in three Epstein-Barr virus-transformed human lymphoblastoid cell lines, each with a different DNA repair phenotype. One cell line lacks O6-alkylguanine-DNA alkyltransferase (AGT) activity; another, derived from a patient with xeroderma pigmentosum, complementation group A, lacks nucleotide excision repair (NER) capability, and the third is competent in both repair functions. ENU-induced toxicity and mutagenicity at the hypoxanthine-guanine phosphoribosyltransferase locus were increased to a similar degree relative to the repair-competent cells in both AGT-deficient and NER-deficient cells. We determined the mutational spectra for ENU by identifying DNA sequence changes at the hypoxanthine-guanine phosphoribosyltransferase locus in at least 26 clones resistant to 6-thioguanine from each cell line. Of the characterized mutations, 89% were single-base pair substitutions. Transitions and transversions were found at AT and GC base pairs in all three cell lines. The biggest difference within the spectra was in the rate of transitions at GC base pairs. Compared to the repair-competent cell line, this mutation was elevated about 8-fold in the AGT-deficient cells and about 3-fold in the NER-deficient cells. We conclude that both AGT and NER play an important role in protecting human cells from the toxic and mutagenic effects of ENU. Furthermore, the mutational spectra suggest that both of these repair systems participate in the repair of O6-ethylguanine adducts.
1 To whom correspondence should be addressed, at Department of Pathology, Campus Box 7095, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Received 3/25/91. Accepted 7/18/91.
This article has been cited by other articles:
|
|
 |
|
  G.J.S. Jenkins, S.H. Doak, G.E. Johnson, E. Quick, E.M. Waters, and J.M. Parry Do dose response thresholds exist for genotoxic alkylating agents? Mutagenesis, November 1, 2005; 20(6): 389 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Baldrich, A. Velazquez, N. Xamena, and O. Cabre Germline mutations induced by N-nitroso-N-ethylurea do not affect the inserted copia retrotransposon in a Drosophila melanogaster wa mutant Mutagenesis, November 1, 2003; 18(6): 527 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Claij, A. van der Wal, M. Dekker, L. Jansen, and H. te Riele DNA Mismatch Repair Deficiency Stimulates N-Ethyl-N-nitrosourea-induced Mutagenesis and Lymphomagenesis Cancer Res., May 1, 2003; 63(9): 2062 - 2066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Madden, M. J. Finegold, and B. L. Slagle Hepatitis B Virus X Protein Acts as a Tumor Promoter in Development of Diethylnitrosamine-Induced Preneoplastic Lesions J. Virol., April 15, 2001; 75(8): 3851 - 3858. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. Singer and B. Hang Nucleic acid sequence and repair: role of adduct, neighbor bases and enzyme specificity Carcinogenesis, June 1, 2000; 21(6): 1071 - 1078. [Full Text] [PDF]
|
|
|
|
 |
|
 W.-D. Chen, J. R. Eshleman, M. R. Aminoshariae, A.-H. Ma, N. Veloso, S. D. Markowitz, W. D. Sedwick, and M. L. Veigl Cytotoxicity and Mutagenicity of Frameshift-Inducing Agent ICR191 in Mismatch Repair-Deficient Colon Cancer Cells J Natl Cancer Inst, March 15, 2000; 92(6): 480 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Dumenco, E Allay, K Norton, and S. Gerson The prevention of thymic lymphomas in transgenic mice by human O6-alkylguanine-DNA alkyltransferase Science, January 8, 1993; 259(5092): 219 - 222. [Abstract] [PDF]
|
|
|
|
 |
|
 J. P. O'Neill DNA damage, DNA repair, cell proliferation, and DNA replication: How do gene mutations result? PNAS, October 10, 2000; 97(21): 11137 - 11139. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
