Journal Article

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

Wim Pauwels, Pavel VodiˇĉČèka, Mario Severi, Kamila Plná, Hendrik Veulemans and Kari Hemminki

in Carcinogenesis

Volume 17, issue 12, pages 2673-2680
Published in print December 1996 | ISSN: 0143-3334
Published online December 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.12.2673
Adduct formation on DNA and haemoglobin in mice intraperitoneally
                    administered with styrene

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Styrene-specific N-7- and O6guanine 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 435 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, ∼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.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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