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Comparative effect of bis-(beta-chloroethyl)-sulfide on basal and differential keratinocytes

Thesis/Dissertation ·
OSTI ID:6597171
Bis-({beta}-Chloroethyl)sulfide (BCES), is a potent alkylating agent and vesicant for human skin. The effect of BCES on basal and differentiated keratinocytes was studied using an epidermal culture and whole rat epidermis. A procedure was developed to expose the epidermal culture and the epidermis topically to various doses of BCES. It was verified autoradiographically that upon application of BCES to the surface of the culture, no spillage into the medium occurred. DNA was determined to be the primary target of BCES by studying the incorporation of {sup 3}H-thymidine, {sup 3}H-uridine and {sup 14}C-leucine after epidermal cultures were exposed to doses of BCES ranging from 10 to 50 nmoles/cm{sup 2}. Hence a parameter related to DNA damage was utilized in determining the sensitivity of the two epidermal cell populations to BCES. This parameter was the nucleoid sedimentation assay, which detects DNA single-strand breaks. The assay indicated that the basal cells are more susceptible to BCES than the differentiated cells. This higher susceptibility was determined to be a consequence of a higher level of alkylation of the basal cell DNA compared to the differentiated cell DNA following exposure to BCES. The level of DNA alkylation was measured using a CsCl density gradient to isolate the DNA.
Research Organization:
Michigan Univ., Ann Arbor, MI (USA)
OSTI ID:
6597171
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
AMINO ACIDS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
AUTORADIOGRAPHY
AZINES
BIOLOGICAL EFFECTS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CELL DIFFERENTIATION
CHALCOGENIDES
COMPARATIVE EVALUATIONS
DNA
EPIDERMIS
EPITHELIUM
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KERATIN
LABELLED COMPOUNDS
LEUCINE
MAMMALS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRIMIDINES
RATS
RIBOSIDES
RODENTS
SCLEROPROTEINS
SENSITIVITY
SKIN
STRAND BREAKS
SULFIDES
SULFUR COMPOUNDS
THYMIDINE
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
URACILS
URIDINE
VERTEBRATES