0000000000809689
AUTHOR
H. Ottenwälder
Covalent Protein Binding of Vinyl Chloride Metabolites During Co-Incubation of Freshly Isolated Hepatocytes and Hepatic Sinusoidal Cells of Rats
Proteins of isolated rat hepatic sinusoidal cells incubated with 14C-vinyl chloride, rat liver microsomes and an NADPH-regenerating system were alkylated by vinyl chloride metabolites formed by microsomes. This suggests that reactive vinyl chloride metabolites can penetrate sinusoidal cells. Protein alkylation in isolated hepatic sinusoidal cells was higher when these were co-incubated with isolated hepatocytes, indicating that reactive vinyl chloride metabolites formed by hepatocytes are stable enough to diffuse out of hepatocytes into sinusoidal cells. Glutathione added to the incubation medium inhibited the covalent protein binding of vinyl chloride metabolites in sinusoidal cells as wel…
Alkylation of RNA by Vinyl Chloride and Vinyl Bromide Metabolites in Vivo: Effect on Protein Biosynthesis
Alkylation of DNA is viewed as representing the initial critical step in carcinogenesis induced by chemical substances. Vinyl chloride and vinyl bromide, compounds with proven carcinogenic potency toward the liver, are biotransformed to reactive metabolites which covalently bind to DNA (see Bolt et al. 1980). Furthermore, extensive covalent binding of metabolites of both vinyl chloride (Laib and Bolt 1977, 1978) and vinyl bromide (Ottenwalder et al. 1979) occurs to RNA of liver when rats are exposed to both vinyl halides. Defined products of alkylation are 1,N6-ethenoadenosine (Laib and Bolt 1777; Ottenwalder et al. 1979) and 3,N4-ethenocytidine (Laib and Bolt 1978; Ottenwalder et al. 1979)…