Some aspects of the metabolism of urethane and N-hydroxyurethane in rodents.
1. Urethane and N-hydroxyurethane are interconvertible in C(-) and C57 mice. 2. In newborn C57/DBA hybrid mice, prior treatment with 3-methylcholanthrene or urethane stimulated the N-hydroxylation of urethane; SKF 525A inhibited the N-hydroxylation at 24hr. but stimulated it at 48hr. after administration. 3. Liver homogenates of CBA and C3H mice, and of Chester Beatty and hooded rats, but not whole-body homogenates of 1-day-old C57/DBA mice or lung homogenate of 3-week-old Chester Beatty rats, metabolized urethane into N-hydroxyurethane in small but definite amounts. 4. Nitrite was detected in the bodies of newborn C57/DBA hybrid mice treated with lethal doses of urethane or N-hydroxyurethane; nitrite formation from N-hydroxyurethane was stimulated by pretreatment of the animals with 3-methylcholanthrene. 5. The rate of catabolism of N-hydroxyurethane by C57/DBA mice was faster in 8-day-old than in 1-day-old animals of the same sex, and faster in females than in males of the same age. 6. Liver slices of several species of rats and mice catabolized N-hydroxyurethane at rates that varied with the age and sex of animals of the same species; liver homogenates or microsomes were less effective than slices from the same liver. 7. The enzyme activity was destroyed by boiling or freezing the liver; it was inhibited by increasing substrate concentration and by urethane, n-butyl carbamate, cyanide, p-benzoquinone or 2,4-dinitrophenol, but not by p-chloromercuribenzoate or menadione. 8. The catabolism of N-hydroxyurethane by liver slices from adult H-strain rats was not oxygen-dependent. 9. Lung homogenates of 4-week-old female Chester Beatty rats catabolized N-hydroxyurethane at 40% of the rate of liver slices from the same source. 10. O-Acetyl- and O-ethoxycarbonyl-N-hydroxyurethane were rapidly deacylated by liver homogenates from adult hooded rats and adult C57 mice, and by human erythrocytes. 11. N-Hydroxyurethane reacted rapidly with pyridoxal phosphate at pH7.4 and 37 degrees . 12. The rate of decomposition of N-hydroxyurethane in 0.1 n-sodium hydroxide was increased by Ni(2+), Cu(2+), Mn(2+) and [Fe(CN)(6)](3-) and decreased by Cr(2+), Zn(2+), Co(2+), Mg(2+) and Fe(2+). 13. Attempts to synthesize sulphonates of N-hydroxyurethane gave ethyl hydrogen sulphate, probably via rearrangement of the unstable O-sulphonate.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002219:Carbamates / Q000378:metabolism* / Q000652:urine; D002729:Chloromercuribenzoates / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D003864:Depression, Chemical; D004140:Dinitrophenols / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008861:Microsomes; D008954:Models, Biological; D009573:Nitrites / Q000378:metabolism; D011335:Proadifen / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D012737:Sex Factors; D013268:Stimulation, Chemical; D013696:Temperature; D013997:Time Factors; D014520:Urethane / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D014639:Vanadium / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology
D002219:Carbamates; D002729:Chloromercuribenzoates; D003486:Cyanides; D004140:Dinitrophenols; D009573:Nitrites; D011809:Quinones; D014639:Vanadium; D014812:Vitamin K; D014520:Urethane; D008748:Methylcholanthrene; D011732:Pyridoxal Phosphate; D011335:Proadifen