Adduct formation on DNA and haemoglobin in mice intraperitoneally administered with styrene

Abstract

Styrene-specific N-7- and O6-guanine DNA adducts and N-terminal valine adducts were determined in mice tissues after the intraperitoneal administration of styrene. Blood, liver, lungs and spleen were collected 3 h after administration of various doses (from 0 to 4.35 mmol/kg b.w.) of styrene. DNA adducts were analysed by the modified 32P-postlabelling assay and N-terminal valine adducts were detected by GC-MS according to the modified Edman degradation technique. In the dose-range studied, for all adducts a clear dose-response relationship was observed. 7-Alkylguanines and O6-styrene guanine adducts were most abundant in lungs, approximately 30% more than in liver and spleen. In all analysed tissues 7-alkylguanines were more abundant than O6-styrene guanine adducts. We found a considerably lower rate of N-terminal valine adduct formation as compared with both DNA adducts. The ratio between 7-alkylguanines and O6-guanine adducts was 1.9, 1.6 and 7.8 in liver, lung and spleen, respectively. In vitro determination of both DNA adducts by 32P-postlabelling resulted also in a lower ratio than that reported earlier using an HPLC analysis. All correlation's between dose, haemoglobin and DNA adducts were very high and significant. However, at the highest injected doses the adduct formation showed a levelling off. To explain this phenomenon a model simulation was performed revealing that 3 h after the injection of the higher doses styrene was not completely converted into styrene-7,8-oxide.

Comparison of DNA‐Reactive Metabolites from Nitrosamine and Styrene Using Voltammetric DNA/Microsomes Sensors

“…Metabolite mediated liver toxicity is a major toxicity pathway [6 – 8, 14]. We recently developed electrochemical and electro-optical sensors capable of detecting reactive metabolites [15 – 20] by employing purified CYPs and DNA films prepared by a layer-by-layer (LbL) technique for high-throughput reactive metabolite screening.…”

Detection of Chemically-Induced Damage in Layered DNA Films with Co(bpy)33+ by Square-Wave Voltammetry

“…In these films, ds-DNA gave near featureless dSWV backgrounds. Oxidation peaks developed as the films were incubated with styrene oxide, which forms known covalent adducts with guanine and adenine bases in DNA [4,23] leading to abnormal molecular genetic events [24,25]. However, disadvantages of this method include voltammetric peaks which must be extracted from background by a derivative, the irreversible nature of the oxidation which limited use of a single electrode to 3 or 4 measurements, and the positive potential (0.7 to 1.1 V vs. SCE) required at which interference from oxidizable materials in the sample might occur.…”

Syntheses of O6‐Alkyl‐ and Arylguanine Derivatives: Nucleobase Adducts Derived from Styrene 7,8‐ and 3,4‐Oxides

“…6 -Guanine adducts derived from 1 have been detected in DNA samples treated with 1, [8,9] in experimental animals [10,11] and in humans exposed to styrene. [12,13] On the other hand, no adducts derived from arene oxides 2-4 have been reported as yet, although it is assumed that styrene 3,4-oxide (2) may contribute significantly to the cytogenetic toxicity of styrene.…”