Macromolecular metabolism of a differentiated rat keratinocyte culture system following exposure to sulfur mustard
A method for producing a stratified, squamous epithelium in vitro by cultivating rat keratinocytes on nylon membranes has been developed in this laboratory. This epidermal-like culture is being used to obtain a better understanding of the mechanism of skin vesication after topical exposure to the sulfur mustard bis(beta-chloroethyl) sulfide (BCES) dissolved in a selected solvent. Radiolabeled macromolecular precursors (thymidine, uridine, and leucine) have been used to study the effect of BCES on the synthesis of DNA, RNA, and protein, respectively, after topical exposure to the mustard at concentrations of 0.01-500 nmol/cm2 dissolved in 70% dimethyl sulfoxide (DMSO). From these and other studies it has been determined that exposure to even the low concentration of 0.01 nmol BCES/cm2 for 30 min results in significant inhibition of (/sup 3/H)thymidine incorporation, although complete recovery occurs by 24 h. Significant inhibition of (/sup 3/H)uridine and (/sup 14/C)leucine incorporation is observed only after exposure to much higher concentrations of BCES (10-500 nmol/cm2). This suggests a very early lesion in macromolecular metabolism with DNA being the primary target.
- Research Organization:
- Univ. of Michigan, Ann Arbor (USA)
- OSTI ID:
- 7066316
- Journal Information:
- J. Toxicol. Environ. Health; (United States), Vol. 23:4
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
CHEMICAL WARFARE AGENTS
METABOLISM
PROTEINS
BIOSYNTHESIS
RNA
ANIMAL CELLS
CARBON 14 COMPOUNDS
CELL CULTURES
DNA
DNA REPLICATION
EPIDERMIS
EPITHELIUM
KERATIN
LEUCINE
RATS
THYMIDINE
TRITIUM COMPOUNDS
URIDINE
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
AZINES
BODY
CARBOXYLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RIBOSIDES
RODENTS
SCLEROPROTEINS
SKIN
SYNTHESIS
TISSUES
URACILS
VERTEBRATES
WEAPONS
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques