Genotoxic activity of chlorohydroxyfuranones in the microscale micronucleus test on mouse lymphoma cells and the unscheduled DNA synthesis assay in rat hepatocytes.
Chlorohydroxyfuranones (CHFs) are mutagenic disinfection by-products found in chlorine-treated drinking water. In the current study, the genotoxicity of four CHFs, 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA), 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), was determined. Two in vitro assays, the microscale micronucleus assay on L5178Y mouse lymphoma cells and the unscheduled DNA synthesis assay on a hepatocyte primary culture from Fisher F344 rats, were carried out. All four CHFs demonstrated genotoxic effects in both assays. In the two systems used, CMCF was the most genotoxic compound, followed by MCA, MX and MCF, respectively. This work was the first study of the DNA damaging properties of all four CHFs in two in vitro genotoxicity tests. These new data expand the range of genetic damages induced by this group of compounds.
Le Curieux
F
F
Department of Organic Chemistry, Abo Akademi University, Biskopsgatan 8, FIN-20500 Turku/Abo, Finland.
Nesslany
F
F
Munter
T
T
Kronberg
L
L
Marzin
D
D
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000633:toxicity*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008223:Lymphoma / Q000473:pathology; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D005663:Furans; D009153:Mutagens; C121895:chlorohydroxyfuranone; D004247:DNA