Metabolic activation in isolated rat hepatocytes. 1990

D A Casciano
Division of Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.

Hepatocytes were exposed in vitro to the hepatocarcinogen N-hydroxy-2-aminofluorene (N-OH-AAF) in order to determine the nature and repair of DNA adducts formed. N-OH-AAF formed 3 DNA adducts, N-(deoxyguanosin-8yl)-2-acetylaminofluorene (dG-C8-AAF), N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), and 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene (dG-N2-AAF). The removal of these adducts was measured up to 38 h following cessation of exposure to N-OH-AAF. The dG-C8-AAF adduct was removed with a half-life of about 10 h, while the other two remained relatively constant throughout the incubation period. The dG-C8-AAF adduct is probably responsible for the induction of unscheduled DNA synthesis (UDS) in this model in vitro system.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003849 Deoxyguanosine A nucleoside consisting of the base guanine and the sugar deoxyribose.
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D005449 Fluorenes A family of diphenylenemethane derivatives.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015073 2-Acetylaminofluorene A hepatic carcinogen whose mechanism of activation involves N-hydroxylation to the aryl hydroxamic acid followed by enzymatic sulfonation to sulfoxyfluorenylacetamide. It is used to study the carcinogenicity and mutagenicity of aromatic amines. 2-Acetamidofluorene,Fluoren-2-ylacetamide,2-AAF,2-Fluorenylacetamide,AAF, Aminofluorene,Acetylaminofluorene,N-2-Fluorenylacetamide,N-Acetyl-2-Aminofluorene,2 Acetamidofluorene,2 Acetylaminofluorene,2 Fluorenylacetamide,Aminofluorene AAF,Fluoren 2 ylacetamide,N 2 Fluorenylacetamide,N Acetyl 2 Aminofluorene

Related Publications

D A Casciano
October 2002, Drug metabolism and disposition: the biological fate of chemicals,
D A Casciano
January 2003, Chemico-biological interactions,
D A Casciano
November 1983, The Biochemical journal,
D A Casciano
September 1991, Toxicology and applied pharmacology,
D A Casciano
June 2005, Drug metabolism and disposition: the biological fate of chemicals,
Copied contents to your clipboard!