Carcinogenesis Advance Access published online on December 23, 2004
Carcinogenesis, doi:10.1093/carcin/bgi007
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1 Cancer Biomarkers and Prevention Group, The Biocentre, University Road, Leicester, LE1 7RH, UK
* To whom correspondence should be addressed. The human population is continually exposed to benzene due to its presence in complex environmental mixtures and exposure has been linked to a range of haematotoxic effects including an increased risk of leukaemia. Several hypotheses have been postulated on how benzene exerts its toxic and carcinogenic effects, one idea being, that following metabolism to more reactive species it can react with DNA to form adducts which subsequently give rise to mutations. Previously, we have demonstrated the formation of four major DNA adducts from the reaction of DNA with the benzene metabolites hydroquinone (HQ) and para-benzoquinone (p-BQ), and the mutagenicity of these adducts when analysed using the supF forward mutation assay after replication in a human kidney cell line. This study demonstrated a potential role in the carcinogenicity of benzene for the DNA adducts formed on 2'-deoxyguanosine 3'-monophosphate. As a continuation of this work, benzene metabolite treated pSP189 plasmid containing the supF reporter gene was transfected into human nucleotide excision repair (NER)-proficient and NER-deficient (Xeroderma pigmentosum, complementation group A) fibroblast cells, to determine the method of adduct repair. For all metabolite treatments in both cell lines the majority of mutations were single base substitutions occurring at GC base pairs, predominantly GC
Received September 3, 2004
Revised December 13, 2004
Accepted December 15, 2004
CARCINOGENESIS
Comparison of the repair of DNA damage induced by the benzene metabolites, hydroquinone and para-benzoquinone. A role for hydroquinone in benzene genotoxicity
Margaret Gaskell, E-mail: mg24{at}le.ac.uk
Abstract 
TA transversions and GCAT transitions. Comparison of mutation frequencies showed a similarity for the HQ treatment for the two cell lines, whereas for the treatments involving p-BQ, an overall higher mutation frequency was observed in the NER-deficient cells compared to the NER-proficient cells. Mutation spectra were significantly different following treatment with HQ in the two cell lines (p = 0.0004). No difference was observed for the control, p-BQ or the combined treatment. The results suggest the involvement of a different repair mechanism for HQ induced DNA damage and further highlights the potential different roles for the two benzene metabolites in benzene mutagenicity.
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