Nitrogen mustard- and half-mustard-induced damage in Escherichia coli requires different DNA repair pathways

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2005-04, Vol.582 (1), p.105-115
• Main Authors: De Alencar, T.A.M., Leitão, A.C., Lage, C.
• Format: Article
• Language: English
• Subjects: Base excision repair; Biological and medical sciences; Escherichia coli; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Medical sciences; Nitrogen mustard; Nucleotide excision repair; Toxicology
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2005.01.004

Bifunctional alkylating agents are used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication. Nitrogen mustards are commonly used chemotherapeutic agents that can bind mono- or bifunctionally to guanines in DNA. Mustard HN1 is considered a monofunctional analog of bifunctional mustard HN2 (mechlorethamine). Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) or base excision repair (BER) were submitted to increasing concentrations of HN2 or HN1, and the results revealed that damage induced by each chemical demands different DNA repair pathways. Damage induced by HN2 demands the activity of NER with a minor requirement of the BER pathway, while HN1 damage repair depends on BER action, without any requirement of NER function. Taken together, our data suggest that HN1 and HN2 seem to induce different types of damage, since their repair depends on distinct pathways in E. coli.