7-Alkylguanine adduct levels in urine, lungs and liver of mice exposed to styrene by inhalation.
This study describes urinary excretion of two nucleobase adducts derived from styrene 7,8-oxide (SO), i.e., 7-(2-hydroxy-1-phenylethyl)guanine (N7alphaG) and 7-(2-hydroxy-2-phenylethyl)guanine (N7betaG), as well as a formation of N7-SO-guanine adducts in lungs and liver of two month old male NMRI mice exposed to styrene by inhalation in a 3-week subacute study. Strikingly higher excretion of both isomeric nucleobase adducts in the first day of exposure was recorded, while the daily excretion of nucleobase adducts in following time intervals reached the steady-state level at 4.32+1.14 and 6.91+1.17 pmol/animal for lower and higher styrene exposure, respectively. beta-SO-guanine DNA adducts in lungs increased with exposure in a linear way (F=13.7 for linearity and 0.17 for non-linearity, respectively), reaching at the 21st day the level of 23.0 adducts/10(8) normal nucleotides, i.e., 0.74 fmol/microg DNA of 7-alkylguanine DNA adducts for the concentration of 1500 mg/m3, while no 7-SO-guanine DNA adducts were detected in the liver after 21 days of inhalation exposure to both of styrene concentrations. A comparison of 7-alkylguanines excreted in urine with 7-SO-guanines in lungs (after correction for depurination and for missing alpha-isomers) revealed that persisting 7-SO-guanine DNA adducts in lungs account for about 0.5% of the total alkylation at N7 of guanine. The total styrene-specific 7-guanine alkylation accounts for about 1.0x10(-5)% of the total styrene uptake, while N1-adenine alkylation contributes to this percentage only negligibly.
Vodicka
Pavel Erik
PE
Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Videnská 1083, 14 220 Prague 4, Czech Republic. pvodicka@biomed.cas.cz
Linhart
Igor
I
Novak
Jan
J
Koskinen
Mikko
M
Vodickova
Ludmila
L
Hemminki
Kari
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000032:analysis / Q000652:urine*; D006147:Guanine / Q000032:analysis / Q000652:urine*; D019570:Inhalation Exposure; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010761:Phosphorus Radioisotopes; D021241:Spectrometry, Mass, Electrospray Ionization; D020058:Styrene / Q000493:pharmacokinetics / Q000633:toxicity*
D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D020058:Styrene; D006147:Guanine