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Polycyclic Aromatic Compounds Mapping

Nucleic Acids Structure and Mapping

  1. Dhrubajyoti Chakravarti

Published Online: 15 SEP 2006

DOI: 10.1002/9780470027318.a1423

Encyclopedia of Analytical Chemistry

Encyclopedia of Analytical Chemistry

How to Cite

Chakravarti, D. 2006. Polycyclic Aromatic Compounds Mapping. Encyclopedia of Analytical Chemistry. .

Author Information

  1. Eppley Institute for Research in Cancer and Allied Diseases, Omaha, USA

Publication History

  1. Published Online: 15 SEP 2006

Abstract

Polycyclic aromatic compounds (PACs) induce tumors by reacting with specific sequences of the initiating oncogene. The resulting DNA damage is converted into oncogenic mutation by in situ mutagenesis during repair or replication. The analysis of PAC/DNA reaction specificity is crucial for understanding the molecular biology of tumor initiation.

The sequence specificity of PAC/DNA reactions has been analyzed by various methods. These methods detect different types of DNA-damage lesions. For example, alkali-labile lesions can be mapped by a chemical procedure (piperidine treatment) and bulky stable adducts can be mapped by a photochemical method (laser-induced strand scission). Biochemical studies have identified several enzymes that act on damaged DNA and can be used for mapping the location of PAC/DNA reactions. For example, DNA lesions block the processive bypass of various enzymes (DNA polymerases, RNA polymerases and exonucleases), whereas some endonucleases (UvrABC exinuclease, S1 nuclease and apurinic/apyrimidinic (AP) endonuclease) make lesion-specific incisions. Therefore, the sites of PAC reactions with DNA are mapped by treating PAC-damaged DNA with these enzymes to generate lesion-specific DNA strand breaks that are resolved by denaturing polyacrylamide gel electrophoresis. More recently, various polymerase chain reactions (PCRs) have been developed for mapping the sequence preferences of PAC/DNA reactions in vivo. These techniques include ligation-mediated polymerase chain reactions (LMPCRs), single-strand ligation polymerase chain reactions (SSLPCRs) and terminal transferase-dependent polymerase chain reactions (TTDPCRs). In these methods, the PCR is used to amplify gene-specific DNA fragments generated by chemical or enzymatic DNA lesion processing.