Action of carbamoylating agents on tumors
Tumor-selective inhibition of protein synthesis by sodium cyanate in vivo may be mediated by cytochrome P-450 dependent metabolism. The authors investigated cyanate metabolism and effects of organic isocyanates under in vivo and in vitro conditions. Homogenates or S9 fractions were incubated with sodium cyanate. There was a decrease in cyanate concentration which was not consistently greater with liver than hepatoma preparations and may be attributed to carbamoylation of proteins. This change was not increased by NADPH and MgCl/sub 2/. When rat liver microsomes were incubated with sodium cyanate no increase in the oxidation of NADPH was detected. Incubation of HTC cells with sodium cyanate (0.25 mg/ml) caused a 10% inhibition of (/sup 3/H)thymidine incorporation into DNA. Inhibitory effects were seen with liver S9 or microsomal preparations and NADPH but in combination with sodium cyanate no more than an additive effect was observed. Ethyl isocyanate and 2-chloroethyl isocyanate caused a greater inhibition of incorporation of (/sup 3/H)leucine in HTC tumors than in host liver but in isolated HTC cells and hepatocytes the effects of the two compounds were similar. Our results do not support but cannot exclude the importance of cyanate metabolism in tumor-selective effects on macromolecular synthesis. The data suggest that these effects may be a common feature of carbamoylating agents.
- Research Organization:
- UMDNJ-New Jersey Medical School, Newark
- OSTI ID:
- 5459304
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
AMINO ACIDS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BODY
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHLORIDES
CHLORINE COMPOUNDS
COENZYMES
CYANATES
CYTOCHROMES
DIGESTIVE SYSTEM
DISEASES
DNA
GLANDS
HALIDES
HALOGEN COMPOUNDS
HEPATOMAS
HETEROCYCLIC COMPOUNDS
IN VITRO
IN VIVO
INHIBITION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUCINE
LIVER
MAGNESIUM CHLORIDES
MAGNESIUM COMPOUNDS
MAMMALS
METABOLISM
MICROSOMES
NADP
NEOPLASMS
NITROGEN COMPOUNDS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PIGMENTS
PROTEINS
PYRIMIDINES
RATS
RIBOSIDES
RODENTS
SODIUM COMPOUNDS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES