Excretion of urinary N7 guanine and N3 adenine DNA adducts in mice after inhalation of styrene

• Published in: Toxicology letters Vol. 184; no. 1; pp. 33 - 37
• Main Authors: Mikeš, Petr, Kořínek, Marek, Linhart, Igor, Krouželka, Jan, Frantík, Emil, Vodičková, Ľudmila, Neufussová, Lenka
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.01.2009; Elsevier
• Subjects: 3-Alkyladenines; 7-Alkylguanines; Adenine - analogs & derivatives; Adenine - urine; Administration, Inhalation; Animals; Biological and medical sciences; Biomarkers of effective dose; Chemical and industrial products toxicology. Toxic occupational diseases; Chromatography, High Pressure Liquid; DNA Adducts - analysis; DNA Adducts - urine; Guanine - analogs & derivatives; Guanine - urine; Male; Medical sciences; Mice; Solvents; Styrene; Styrene - administration & dosage; Styrene - metabolism; Toxicology; Urinary DNA adducts; Urinary DNA adducts; 7-Alkylguanines; Biomarkers of effective dose; 3-Alkyladenines; Styrene; Urine; Excretion; Rodentia; Adenine; Biological marker; B-Vitamins; Guanine; Inhalation; Organic solvent; Vertebrata; Mammalia; Mouse; Animal; DNA; Effective dose; Molecular adduct
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2008.10.010

New urinary adenine adducts, 3-(2-hydroxy-1-phenylethyl)adenine (N3αA), 3-(2-hydroxy-2-phenylethyl)adenine (N3βA), were found in the urine of mice exposed to styrene vapour. These styrene 7,8-oxide derived adenine adducts as well as previously identified guanine adducts, 7-(2-hydroxy-1-phenylethyl)guanine (N7αG) and 7-(2-hydroxy-2-phenylethyl)guanine (N7βG) were quantified by HPLC–ESI–MS 2 and the excretion profile during and after a repeated exposure to 600 mg/m 3 or 1200 mg/m 3 of styrene for 10 consecutive days (6 h/day) was determined. The excretion was dose dependent. Total N3 adenine adducts (N3αA + N3βA) excreted amounted to nearly 0.8 × 10 −5% of the absorbed dose while urinary N7 guanine adducts (N7αG + N7βG) amounted to nearly 1.4 × 10 −5% of the dose. No accumulation of the adducts was observed. Due to rapid depurination from the DNA, the excretion of both N3 adenine and N7 guanine adducts ceased shortly after finishing the exposure. Both N3 adenine and N7 guanine adducts may be used as non-invasive biomarkers of effective dose reflecting only a short time exposure to styrene.