Journal article
Differential repair of polycyclic aromatic hydrocarbon DNA adducts from an actively transcribed gene
DNA repair, Vol.9(9), pp.1011-1016
2010
Handle:
https://hdl.handle.net/2376/113918
PMID: 20634147
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are carcinogens with varying potencies. These compounds are metabolized to diol epoxides that react to form DNA adducts. Nucleotide excision repair is a critical cellular defense against these bulky DNA adducts which, if not repaired, can lead to mutations and the initiation of cancer. The structural features of the PAH-adducts play a role in differential repair of these adducts by the global genomic repair subpathway of nucleotide excision repair. DNA adducts derived from the PAHs containing bay-regions are repaired more rapidly than adducts derived from PAHs containing fjord-regions. We have employed the host cell reactivation assay to examine the rate of repair of these adducts in an actively transcribing gene. The pGL3 plasmid containing a luciferase gene was damaged with diol epoxides of benzo[
a]pyrene (B[
a]P-DE), dibenzo[
a,l]pyrene (DB[
a,l]P-DE), benzo[g]chrysene (B[g]Ch-DE), and benzo[
c]phenanthrene (B[
c]Ph-DE). The plasmids were transfected into B-lymphocytes with normal repair capacity as well as lymphocytes derived from patients with the XP-A, XP-C and CS-B syndromes. We found that XPA cells were able to transcribe slowly past B[g]Ch-adducts but not the other PAHs. Using the amount of luciferase produced as a measure of DNA repair, we found that the relative rates of repair in the actively transcribing luciferase gene was B[
a]P-DE
>
DB[
a,l]P-DE, B[
g]Ch-DE, >B[
c]Ph-DE in repair proficient and XP-C cells. These results indicate that the abilities to transcribe past and to repair the PAH adducts are dependent on different structural features of the DNA adducts.
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Details
- Title
- Differential repair of polycyclic aromatic hydrocarbon DNA adducts from an actively transcribed gene
- Creators
- Qing Zhong - Department of Biochemistry & Molecular Biology, Pennsylvania State University, 500 University Dr, Hershey, PA 17033, USAShantu Amin - Department of Pharmacology, Pennsylvania State University, 500 University Dr, Hershey, PA 17033, USAPhilip Lazarus - Department of Pharmacology, Pennsylvania State University, 500 University Dr, Hershey, PA 17033, USAThomas E Spratt - Department of Biochemistry & Molecular Biology, Pennsylvania State University, 500 University Dr, Hershey, PA 17033, USA
- Publication Details
- DNA repair, Vol.9(9), pp.1011-1016
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- Elsevier B.V
- Identifiers
- 99900547966001842
- Language
- English
- Resource Type
- Journal article