Absorption of 3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H] furanone (MX) through rat small intestine in vitro.
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.
Clark
N W
NW
School of Biochemistry, University of Birmingham, Edgbaston, UK.
Chipman
J K
JK
D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000378:metabolism* / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D005663:Furans; D009153:Mutagens; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; D005978:Glutathione