Bibliographic Citation
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Title | Apoptosis (programmed cell death) as an indicator of xenobiotic toxicity |
Creator/Author | Bond, G.P. |
Publication Date | 1989 Jan 01 |
OSTI Identifier | OSTI ID: 5524395 |
Resource Type | Miscellaneous |
Resource Relation | Thesis (Ph. D.) |
Research Org | Kansas Univ., Lawrence, KS (USA) |
Subject | 560300 -- Chemicals Metabolism & Toxicology ;550501 -- Metabolism-- Tracer Techniques; LIVER-- NECROSIS;XENOBIOTICS-- TOXICITY; BIOLOGICAL INDICATORS;CHICKENS;DNA REPLICATION;DOSE-RESPONSE RELATIONSHIPS;MICE;THYMIDINE;TIME DEPENDENCE;TRACER TECHNIQUES;TRITIUM COMPOUNDS |
Related Subject | ANIMALS;AZINES;BIRDS;BODY;DIGESTIVE SYSTEM;FOWL;GLANDS;HETEROCYCLIC COMPOUNDS;HYDROGEN COMPOUNDS;ISOTOPE APPLICATIONS;MAMMALS;NUCLEIC ACID REPLICATION;NUCLEOSIDES;NUCLEOTIDES;ORGANIC COMPOUNDS;ORGANIC NITROGEN COMPOUNDS;ORGANS;PATHOLOGICAL CHANGES;PYRIMIDINES;RIBOSIDES;RODENTS;VERTEBRATES |
Description/Abstract | Xenobiotics alter the frequency and pattern of apoptosis (programmed cell death).^Preliminary studies identified the mouse liver, with normally low levels of apoptosis, as a preferable test system to the chicken embryo limb, with normally high levels of apoptosis.^The major purposes of these investigations, using the apoptogen and necrogen 1,1-dichloroethylene (DCE), were to determine if increases in apoptosis, (1) could be quantified as a direct result of treatment, (2) were dose- and time-dependent, (3) were independent of necrosis, (4) were associated with mitosis in the control of cell numbers and (5) were limited to specific areas of the liver.^To these ends, food-deprived female, CF-1 mice were administered DCE ip under varying experimental conditions.^Increased apoptosis occurred in a dose- and time-dependent manner after treatment with 12.5, 40, and 125 mg/kg for 0.5, 1, 2, 4 and 8 hr.^Peak effects were observed at 4 hr.^Apoptosis occurred only in the midzonal/pericentral areas of the liver.^At 12.5 mg/kg, there were no effects on biochemical (alanine transaminase) and morphological indices of necrosis, establishing apoptosis as a separate phenomenon from necrosis.^Increased {sup 3}H-thymidine incorporation (DNA synthesis), mitosis and the percentage of octaploid hepatocytes occurred from 24-48 hr after treatment with the apoptotic but non-necrotic dose of 40 mg/kg.^Apoptosis only occurred in the midzonal/pericentral areas of the liver after multiple doses with DCE, indicating the zonal selectivity of the response.^In conclusion, apoptosis, a normally occurring homeostatic process associated with mitosis in the control of cell numbers, is affected by selected xenobiotics in a dose-dependent manner.^Xenobiotic-induced apoptosis in the liver occurs at low doses of xenobiotics which cause no other effects on tissue structure or function. |
Publisher | Lawrence, KS (US) ;Univ. of Kansas |
Country of Publication | United States |
Language | English |
Format | Pages: (213 p) |
Availability | University Microfilms, PO Box 1764, Ann Arbor, MI 48106, Order No.90-09,862 |
System Entry Date | 2001 May 13 |
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