DNA is frequently damaged by endogenous agents inside the cells. Some exogenous agents such as polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment and may thus contribute to the 'background' DNA damage in humans. DNA lesions are normally removed by various repair mechanisms. The major repair mechanisms for various DNA lesions are summarized. In contrast to the extensively studied repair mechanisms, much less is known about the relative repair efficiencies of various DNA lesions. Since DNA repair is a crucial defense against carcinogenesis, it may constitute an important factor affecting the carcinogenicity of DNA damaging agents. We have adopted a human cell-free system for measuring relative DNA repair efficiencies based on the concept of repair competition between acetylaminofluorene adducts and other DNA lesions of interest. Using this in vitro system, we determined the relative repair efficiencies of PAH adducts induced by: anti-(±)-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE), anti-(±)-benz[a]anthracene-trans-3,4-dihydrodiol-1,2-epoxide (BADE-I), anti-(±)-benz[a]anthracene-trans-8,9-dihydrodiol-10,11-epoxide (BADE-II), anti-(±)-benzo[b]fluoranthene-trans-9,10-dihydrodiol-11,12-epoxide (BFDE), anti-(±)-chrysene-trans-1,2-dihydrodiol-3,4-epoxide (CDE), and anti-(±)-dibenzo[a,l]pyrene-trans-11,12-dihydrodiol-13,14-epoxide (DBPDE). While damage by BPDE, DBPDE, CDE, and BFDE were repaired by nucleotide excision repair as efficiently as AAF adducts, the repair of BADE-I and BADE-II adducts were significantly slower in human cell extracts. Damage by DBPDE at 3 μM in vitro yielded ~5-fold higher DNA adducts than BPDE as determined by quantitative PCR. This potent DNA reactivity may account in part for the potent carcinogenicity of dibenzo[a,l]pyrene. The correlation of these results to the carcinogenic properties of the PAH compounds is discussed. Furthermore, we show that NER plays a role in AP site repair in vivo in the eukaryotic model organism yeast. Copyright (C) 1999 Elsevier Science B.V.
|Number of pages||13|
|Journal||Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis|
|State||Published - Mar 8 1999|
Bibliographical noteFunding Information:
We thank Errol Friedberg for providing us with human cell lines. These studies were supported by a start-up fund from the University of Kentucky, a Tobacco and Health Research Institute grant from the University of Kentucky and a NIH grant CA67978. This publication was made possible by a predoctoral fellowship to E.B. (ES5796) from the National Institute of Environmental Health Sciences (NIEHS, NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIEHS.
- Cell-free system
- DNA repair
ASJC Scopus subject areas
- Molecular Biology
- Health, Toxicology and Mutagenesis