Inhibition of the metabolism of urethane in the mouse by dimethyl sulfoxide (DMSO).
Previous studies from this laboratory have shown that alcohols inhibit the localization of nitrosonornicotine and urethane in tissues of the mouse. Subsequent studies demonstrated that this inhibition of the localization of urethane was apparently due to an almost total inhibition of the metabolism of that compound by ethanol. We now report that dimethyl sulfoxide (DMSO) also almost completely inhibits the localization of urethane metabolites in tissues of the mouse and maintains a high concentration of urethane in blood. Since metabolism is essentially the only route of elimination of urethane in the mouse, this indicates that DMSO inhibits the metabolism of urethane. These studies lend further support to the suggestion that urethane is metabolized by either an alcohol dehydrogenase, an aldehyde dehydrogenase, or an alcohol-preferring isozyme of cytochrome P-450. These results indicate that studies on the metabolism as well as the carcinogenic activity of urethane (and possibly other chemicals) also may be affected by concurrent administration of DMSO.
Waddell
W J
WJ
Department of Pharmacology and Toxicology, University of Louisville, Kentucky 40292.
Marlowe
C
C
Yamamoto
T
T
Clark
M J
MJ
D000818:Animals; D001345:Autoradiography; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D014018:Tissue Distribution; D014520:Urethane / Q000378:metabolism* / Q000493:pharmacokinetics; D014916:Whole-Body Irradiation
D014520:Urethane; D004121:Dimethyl Sulfoxide