Adduct formation on DNA and haemoglobin in mice intraperitoneally administered with styrene.
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.
Pauwels
W
W
Laboratory for Occupational Hygiene and Toxicology, Katholieke Universiteit Leuven, Belgium.
Vodicèka
P
P
Severi
M
M
Plná
K
K
Veulemans
H
H
Hemminki
K
K
D000818:Animals; D018736:DNA Adducts / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D013343:Styrenes / Q000378:metabolism*
D018736:DNA Adducts; D004852:Epoxy Compounds; D006454:Hemoglobins; D013343:Styrenes; C013690:styrene oxide