Detection of in vivo genotoxicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) by the alkaline single cell gel electrophoresis (Comet) assay in multiple mouse organs.
We tested the genotoxicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) in the mouse in 6 organs (liver, lung, kidney, brain, spleen, and bone marrow) and in the mucosa of stomach, jejunum, ileum, colon, and bladder using the alkaline single-cell gel electrophoresis (SCG) (Comet) assay modified by us. Mice were sacrificed 1, 3, 6, and 24 h after oral administration of the mutagen at 100 mg/kg. MX yielded statistically significant DNA damage in the liver, kidney, lung, and brain and in all the mucosa samples. While DNA damage persisted in the gastrointestinal and urinary tract for 6-24 h after a single oral dosing, it peaked in the liver at 1 h and returned to almost the control level at 3 h. Our present results suggest that MX is genotoxic for various mouse organs, but not for the hematopoietic system, and that the alkaline SCG assay with a homogenization technique can be used to predict genotoxicity in the gastrointestinal and urinary tracts.
Sasaki
Y F
YF
Laboratory of Genotoxicity, Faculty of Chemical and Biological Engineering, Hachinohe National College of Technology, Aomori, Japan. yfsasaki-c@hachinohe-ct.ac.jp
Nishidate
E
E
Izumiyama
F
F
Watanabe-Akanuma
M
M
Kinae
N
N
Matsusaka
N
N
Tsuda
S
S
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D004249:DNA Damage; D004064:Digestive System / Q000187:drug effects; D004586:Electrophoresis / Q000379:methods; D005663:Furans / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D009928:Organ Specificity; D013154:Spleen / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects
D005663:Furans; D009153:Mutagens; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone