Journal article
Interaction of benzoquinone- and hydroquinone-derivatives of lower chlorinated biphenyls with DNA and nucleotides in vitro
Chemico-biological interactions, Vol.142(3), pp.307-316
2003
DOI: 10.1016/S0009-2797(02)00141-2
PMID: 12453668
Abstract
Commercial polychlorinated biphenyls (PCBs) are complete carcinogens in rodents, however, their initiating (DNA damaging) activity has not been conclusively demonstrated. In the present study, we reacted synthetic 2-phenyl-1,4-benzoquinones (BQ) and 2-phenyl-1,4-hydroquinones (HQ) of 2-chloro-, 3-chloro-, 4-chloro-, 3,4-dichloro-, and 3,4,5-trichlorobiphenyls with calf thymus DNA and individual deoxynucleoside-3′-monophosphates for 4 h at 37
°C. Analysis of DNA adducts resulting from BQ and HQ derivatives of the test congeners by
32P-postlabeling showed essentially similar adduct patterns. However, the adduct pattern and reactivity differed with the congener used. Quantitatively, 2-chloro-BQ/HQ produced in the highest DNA adduct levels and 3,4,5-chloro-BQ/HQ was the least reactive. Chromatographic comparison of DNA and nucleotide adducts derived from 4-chloro-BQ revealed that cytosine, adenine, and thymidine in the DNA accounted for most of the DNA adducts. Interestingly, none of the adducts in DNA were guanine-derived, even though this mononucleotide was highly reactive. These results suggest that both BQ and HQ derivatives of PCBs are capable of covalently binding to DNA, and chromatographic similarity in adduct patterns resulting from these two metabolites suggest possible involvement of intermediary semiquinone radicals. Experiments are underway to determine their in vivo significance.
Details
- Title: Subtitle
- Interaction of benzoquinone- and hydroquinone-derivatives of lower chlorinated biphenyls with DNA and nucleotides in vitro
- Creators
- Jamal M Arif - Department of Preventive Medicine and Environmental Health, University of Kentucky Medical Center, Lexington, KY 40536-0305, USAHans-Joachim Lehmler - Graduate Center for Toxicology, University of Kentucky Medical Center, Lexington, KY 40536-0305, USALarry W Robertson - Graduate Center for Toxicology, University of Kentucky Medical Center, Lexington, KY 40536-0305, USARamesh C Gupta - Department of Preventive Medicine and Environmental Health, University of Kentucky Medical Center, Lexington, KY 40536-0305, USA
- Resource Type
- Journal article
- Publication Details
- Chemico-biological interactions, Vol.142(3), pp.307-316
- DOI
- 10.1016/S0009-2797(02)00141-2
- PMID
- 12453668
- NLM abbreviation
- Chem Biol Interact
- ISSN
- 0009-2797
- eISSN
- 1872-7786
- Publisher
- Elsevier Ireland Ltd
- Language
- English
- Date published
- 2003
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute
- Record Identifier
- 9984001093702771
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