Abstract:
:There is increasing concern that compounds formed during the chemical or biological transformation of pollutants in the environment may be more detrimental to human and environmental health than the original pollutant. In this study, two bacterial transformation products of polycyclic aromatic hydrocarbons (PAHs), pyrene-4,5-quinone (P45Q) and fluoranthene-2,3-quinone (F23Q), were evaluated for mutagenicity by measuring aldehydic DNA lesions (ADL) in calf thymus DNA and HeLa S3 cells. Both quinones caused oxidative DNA damage in vitro through a copper-mediated redox cycle and subsequent production of reactive oxygen species (ROS). Hydrogen peroxide and copper were essential for causing oxidative DNA damage and glutathione (GSH) prevented DNA damage from F23Q better than from P45Q. In experiments using HeLa cells, F23Q decreased cell viability, but did not produce measurable levels of ADL or base oxidation. To test the hypothesis that DNA damage was being prevented by conjugation of F23Q with GSH, GSH-depleted cells were treated with both quinones. GSH depletion did not increase the toxicity of F23Q or cause it to oxidize DNA. Treatment of HeLa cells with metal chelators did not decrease F23Q toxicity. It is therefore possible that F23Q affected cell viability through a ROS-independent mechanism, either by conjugation with essential cellular proteins or through cellular or mitochondrial membrane damage, which precluded oxidation of DNA. In contrast, P45Q caused both ADL and base oxidation in cells. Neocuproine reduced the amount of ADL caused by P45Q, indicating that copper was still important for the intracellular generation of damaging oxidants. P45Q is a novel metabolite and its effects on DNA have not been investigated previously. This study exemplifies the importance of considering not only primary environmental pollutants, but also their biologically or chemically generated transformation products.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Zielinska-Park J,Nakamura J,Swenberg JA,Aitken MDdoi
10.1093/carcin/bgh174keywords:
subject
Has Abstractpub_date
2004-09-01 00:00:00pages
1727-33issue
9eissn
0143-3334issn
1460-2180pii
bgh174journal_volume
25pub_type
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