Genotoxicity of the benzene metabolites para-benzoquinone and hydroquinone.
Our interest in benzene-DNA adduct formation and their consequence has led us to develop a number of sensitive methods for their analysis. A HPLC method for the analysis of 32P-postlabelled benzene-DNA adducts was developed and used to detect adducts formed from the reaction of DNA or individual deoxynucleotides with the metabolites para-benzoquinone (p-BQ) and hydroquinone (HQ). Reaction of DNA with BQ yielded four adducts, the major product being a deoxycytidine adduct. HQ formed a single detectable deoxyguanosine DNA adduct, which was a minor product of the reaction of DNA with p-BQ. The supF forward mutation assay was used to assess the mutagenicity of p-BQ and HQ after transfection of treated plasmid in the human kidney cell line, Ad293. Single base substitution mutations at GC base pairs (bp) predominated for each treatment. However, when the mutation spectra achieved for each treatment were compared they were shown to be significantly different (p=0.004). These results may suggest either a possible role for the minor benzene-deoxyguanosine adducts in benzene genotoxicity or that HQ is causing DNA modification via a different mechanism, such as oxidative damage.
Gaskell
Margaret
M
Cancer Biomarkers and Prevention Group, The Biocentre, Leicester University, University Road, Leicester LE1 7RH, UK. mg24@le.ac.uk
McLuckie
Keith I E
KI
Farmer
Peter B
PB
D001554:Benzene / Q000378:metabolism; D016227:Benzoquinones / Q000378:metabolism / Q000633:toxicity*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018736:DNA Adducts; D016153:Genes, Suppressor; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism / Q000633:toxicity*; D009152:Mutagenicity Tests; D010761:Phosphorus Radioisotopes; D012343:RNA, Transfer / Q000235:genetics
D016227:Benzoquinones; D018736:DNA Adducts; D006873:Hydroquinones; D010761:Phosphorus Radioisotopes; C096275:supF tRNA; C004532:quinone; D012343:RNA, Transfer; D001554:Benzene; C031927:hydroquinone