Oxidative DNA damage in tissues of English sole (Parophrys vetulus) exposed to nitrofurantoin.
Juvenile English sole were exposed intramuscularly to nitrofurantoin (NF) and the levels of 8-hydroxy-2' deoxyguanosine (8-OH-dG) in liver, kidney and blood were determined using reversed-phase HPLC with electrochemical detection. Identification and quantitation of the 8-OH-dG in the samples was accomplished by comparison with standard 8-OH-dG, which was characterized by UV spectroscopy and fast-atom bombardment mass spectrometry. The levels of hepatic 8-OH-dG increased (r2 = 0.59, P = 0.015) with the dose of NF (0.10-10 mg NF/kg fish). In kidney and blood, however, the levels of 8-OH-dG were significantly higher than controls only at the highest dose tested. The level of binding in liver ranged from 0.37 to 0.76 fmol 8-OH-dG/micrograms DNA. The levels of hepatic 8-OH-dG reached a maximum (approx. 1 fmol 8-OH-dG/micrograms DNA) between 1 and 3 days after exposure, followed by a decrease to control levels (approx. 0.25 fmol 8-OH-dG/micrograms DNA) at 5 days post-exposure. These data demonstrate the first direct evidence for the formation of oxidized DNA bases resulting from the metabolism of a nitroaromatic compound by fish.
Nishimoto
M
M
Environmental Conservation Division, National Oceanic and Atmospheric Administration, Seattle, WA 98112-2097.
Roubal
W T
WT
Stein
J E
JE
Varanasi
U
U
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000378:metabolism; D005412:Flatfishes / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry; D009582:Nitrofurantoin / Q000633:toxicity*; D010084:Oxidation-Reduction; D013056:Spectrophotometry, Ultraviolet
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D009582:Nitrofurantoin; D003849:Deoxyguanosine