Energy Citations Database

Bibliographic Citation

 
Document
For copies of Journal Articles, please contact the Publisher or your local public or university library and refer to the information in the Resource Relation field.
For copies of other documents, please see the Availability, Publisher, Research Organization, Resource Relation and/or Author (affiliation information) fields and/or Document Availability.
Title Apoptosis (programmed cell death) as an indicator of xenobiotic toxicity
Creator/Author Bond, G.P.
Publication Date1989 Jan 01
OSTI IdentifierOSTI ID: 5524395
Resource TypeMiscellaneous
Resource RelationThesis (Ph. D.)
Research OrgKansas Univ., Lawrence, KS (USA)
Subject560300 -- 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 SubjectANIMALS;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.
PublisherLawrence, KS (US) ;Univ. of Kansas
Country of PublicationUnited States
LanguageEnglish
FormatPages: (213 p)
AvailabilityUniversity Microfilms, PO Box 1764, Ann Arbor, MI 48106, Order No.90-09,862
System Entry Date2001 May 13

Top