Kinetics of formation of specific styrene oxide adducts in double-stranded DNA

Mikko Koskinen, Ludmila Vodičková, Pavel Vodička, Susan C. Warner, Kari Hemminki

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    The possible carcinogenicity of styrene is believed to be related to the DNA-binding properties of styrene 7,8-oxide (SO). In order to compare the intrinsic reactivity of the different nucleophilic sites in DNA towards SO and to evaluate the candidates for human biomonitoring we have determined the second-order rate constants and stabilities of several SO-adducts in double-stranded DNA. These include α- and β-isomers of N7-substituted and αN2-substituted guanines, α- and βN3-substituted and αN6-substituted adenines as well as βN3- and αN4-substituted cytosines. The highest rate constants were found for the spontaneously depurinating N7-guanines being ca. 3-15-fold higher than those for the stable adducts. When the relative proportions of different alkylation products were determined in course of time, after a single addition of SO, the labile N7-guanines and N3-adenines were the major products at early time points. After 144 h of incubation at 37°C, αN6-SO-adenine and αN2-SO-guanine as well as βN3-SO-uracil were the major adducts. Regarding human biomonitoring, the N7-substituted guanines should be one of the main targets because of the high reactivity of the N7-atom of guanine. However, in the case of chronic styrene exposures the chemically more stable DNA adducts may become important.

    Original languageEnglish (US)
    Pages (from-to)111-124
    Number of pages14
    JournalChemico-Biological Interactions
    Issue number2
    StatePublished - Nov 28 2001


    • Biomonitoring
    • DNA adducts
    • Styrene
    • Styrene 7,8-oxide

    ASJC Scopus subject areas

    • Toxicology

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    Koskinen, M., Vodičková, L., Vodička, P., Warner, S. C., & Hemminki, K. (2001). Kinetics of formation of specific styrene oxide adducts in double-stranded DNA. Chemico-Biological Interactions, 138(2), 111-124.