Effect of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD) in vitro on RNA synthesis in rat thymocytes

Conference · Mon Mar 11 00:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5307440

Olnes, M; Abraham, M; Kurl, R N ^[1]

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1. Brown Univ., Providence, RI (United States)

TCDD, a potent inducer of cytochrome P-450, augments synthesis of specific liver constituents while simultaneously causing marked involution of the thymus. To elucidate the mechanism by which TCDD induces thymic atrophy, initial experiments were performed to establish the kinetics of uptake of TCDD in vitro by thymocytes. The latter were incubated with either {sup 3}H-TCDD or TCDD for various time intervals. Measurement of radio-activity and gel mobility shift assays using nuclear extracts and a dioxin-responsive element (DRE-3) of the cytochrome P-450 (Cyplal) gene revealed maximum uptake of TCDD by thymocyte nuclei at 30-60 min post incubation. RNA synthesis was increased as early as 30 min. The increase in RNA synthesis could be inhibited by actinomycin D. At these time points degradation of DNA was visible. Whether newly formed RNA is translated into a protein(s) which in turn is (are) responsible for degradation of DNA leading to cell death needs to be established.

• OSTI ID: 5307440
• Report Number(s): CONF-9104107-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:4; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
DIOXIN
BIOLOGICAL EFFECTS
RNA
BIOSYNTHESIS
THYMOCYTES
PATHOLOGICAL CHANGES
ACTINOMYCIN
IN VITRO
METABOLISM
MIXED-FUNCTION OXIDASES
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
DRUGS
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PROTEINS
RODENTS
SOMATIC CELLS
SYNTHESIS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology