Disease relevance of Chloroethylisocyanate

• The effects of 2-chloroethylisocyanate, ethylisocyanate and sodium cyanate on the uptake of isotope-labeled thymidine, leucine and H2O were compared in rat liver and hepatomas [1].

High impact information on Chloroethylisocyanate

• As model reactions, several O-substituted derivatives were prepared by alkylation of (RS)-17 with benzyl chloride and condensation of (RS)-17 with butyl isocyanate and (S)-17 with 2-chloroethyl isocyanate [2].
• The antitumor, DNA-alkylating agent 1,3-bis[2-chloroethyl]-2-nitrosourea (BCNU; Carmustine), which generates 2-chloroethyl isocyanate upon decomposition in situ, inhibits cellular glutathione reductase (GR; EC 1.8.1.7) activity by up to 90% at pharmacological doses [3].
• Glutathione and N-acetylcysteine conjugates of 2-chloroethyl isocyanate. Identification as metabolites of N,N'-bis(2-chloroethyl)-N-nitrosourea in the rat and inhibitory properties toward glutathione reductase in vitro [4].
• For example, CNCC-(S) in phosphate buffer, pH 7.0, and 37 degrees gave rise to 2-chloroethylisocyanate, bis(2-chloroethyl)urea and bis(2-hydroxyethyl)disulfide, whereas in the presence of DTT it afforded 2-chloroethylisocyanate, bis(2-chloroethyl)urea, bis(2-hydroxyethyl) disulfide, thiirane and 2-mercaptoethanol [5].
• The same nitrosoureas and, in addition, 2-chloroethyl isocyanate inhibited an A24 lyase-containing cytoplasmic extract in cleaving protein A24 into histone H2A and ubiquitin [6].

Chemical compound and disease context of Chloroethylisocyanate

• In contrast to the insensitivity of hepatomas to dietary modulation of nucleotide levels, treatment of hepatoma-bearing rats with carbamoylating agents (sodium cyanate and 2-chloroethyl isocyanate) caused decreases in the levels of nucleotides in the tumors which were generally greater than in host livers [7].

Biological context of Chloroethylisocyanate

• Chloroethylisocyanate was active only in the absence of excision repair, suggesting that efficient DNA repair is the cause for the weak genotoxic effectiveness of these genotoxins [8].

Associations of Chloroethylisocyanate with other chemical compounds

• Such enzymes, glutathione reductase, chymotrypsin and gamma-glutamyltranspepidase are not inhibited by CCRG 81010 under conditions where BCNU and 2-chloroethyl isocyanate show complete inhibition of enzyme activity, suggesting an absence of carbamoylating species [9].
• Reaction of a Kdo derivative with 2-chloroethyl isocyanate in the presence of DMAP gave an alpha-spiro product (82%) and an alpha-Kdo derivative of a dimeric isocyanate adduct (10%) [10].

Gene context of Chloroethylisocyanate

• Inhibition of precursor uptake is also not produced by concentrations of 2-chloroethylisocyanate that inhibit intracellular glutathione reductase activity [9].

References