Absorption of 3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H] furanone (MX) through rat small intestine in vitro. 1995

N W Clark, and J K Chipman
School of Biochemistry, University of Birmingham, Edgbaston, UK.

The intestinal absorption of 3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H] furanone (MX), a highly mutagenic furanone found in chlorinated waters, was studied using an in vitro everted rat gut sac system, using reverse mutation in Salmonella typhimurium to detect mutagens transported from the mucosal to the serosal compartments. Absorption was measurable, but limited, with significant increase in bacterial revertants (serosal compartment) noted at a dose of 50 micrograms/ml MX (mucosal compartment, p < 0.05). Gut sac incubation with MX and glutathione (GSH, 1.0 mM) resulted in no detectable absorption of mutagens. Preincubation with diethylmaleate to deplete mucosal GSH resulted in increased absorption of MX-derived mutagens compared to controls (a significant induction of revertant colonies was noted at a dose of 25 micrograms/ml MX p < 0.05). Gut sac incubation with chlorinated fulvic acids resulted in no detectable absorption of mutagens. In vitro studies to assess the possibility of beta-lyase activation of the postulated MX-GSH conjugate showed no mutagenic activation.

UI MeSH Term Description Entries
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D007421 Intestine, Small The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM. Small Intestine,Intestines, Small,Small Intestines
D008297 Male Males
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005663 Furans Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran. Tetrahydrofurans
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining

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