Biomaterial Database

Effects of adduct formation on the biological activity of single- and double-stranded øX174 DNA, modified by N-acetoxy-N-acetyl-2-aminofluorene. 1984

J T Lutgerink, and J Retèl, and H Loman

In order to establish a good quantitative relationship between the number of acetylaminofluorene adducts and the extent of inactivation of DNA, single-stranded (ss) øX174 DNA and øX174 RF DNA were modified to various extents with 3H-labelled N-acetoxy-N-acetyl-2-aminofluorene (N-AcO-AAF) and subsequently transfected to Escherichia coli spheroplasts having different repair capabilities. Exponential survival curves were obtained. In the case of ssDNA about one adduct per molecule appears to be lethal. On the other hand only 1 out of 10.2 adducts is found to inactivate RF DNA if tested on wild-type E. coli. However, when assayed on strains deficient in excision repair 1 out of 2.3 adducts leads to inactivation of RF DNA. RecA-dependent postreplication repair only has little influence on these figures. Product analysis of the modified DNAs shows that in RF DNA at least 76% of the interaction products is N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene (dGuo-C8-AAF) and at least 6% and at most 12% is 3-(deoxyguanosin-N2-yl)-N-acetyl-2-aminofluorene (dGuo-N2-AAF). In ssDNA only dGuo-C8-AAF is formed. No apurinic sites could be detected in the modified DNAs. From these results it can be concluded that in RF DNA most of the dGuo-C8-AAF is removed by excision repair. The remaining damage, consisting probably both of dGuo-N2-AAF and unexcised dGuo-C8-AAF, inactivates RF DNA. Inactivation can be explained by a model which shows that only damage in the minus strand of RF DNA inhibits replication and/or transcription.

UI	MeSH Term	Description	Entries
D010584	Bacteriophage phi X 174	The type species of the genus MICROVIRUS. A prototype of the small virulent DNA coliphages, it is composed of a single strand of supercoiled circular DNA, which on infection, is converted to a double-stranded replicative form by a host enzyme.	Coliphage phi X 174,Enterobacteria phage phi X 174,Phage phi X 174,phi X 174 Phage,Phage phi X174
D002621	Chemistry	A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D004277	DNA, Single-Stranded	A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.	Single-Stranded DNA,DNA, Single Stranded,Single Stranded DNA
D004279	DNA, Viral	Deoxyribonucleic acid that makes up the genetic material of viruses.	Viral DNA
D000099	Acetoxyacetylaminofluorene	An alkylating agent that forms DNA ADDUCTS at the C-8 position in GUANINE, resulting in single strand breaks. It has demonstrated carcinogenic action.	Acetoxyacetamidofluorene,Acetoxyfluorenylacetamide,N-Acetoxy-2-acetylaminofluorene,N-Acetoxy-N-acetyl-2-aminofluorene,N Acetoxy 2 acetylaminofluorene,N Acetoxy N acetyl 2 aminofluorene
D001080	Apurinic Acid	Hydrolysate of DNA in which purine bases have been removed.	Acid, Apurinic
D014779	Virus Replication	The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.	Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
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
D055598	Chemical Phenomena	The composition, structure, conformation, and properties of atoms and molecules, and their reaction and interaction processes.	Chemical Concepts,Chemical Processes,Physical Chemistry Concepts,Physical Chemistry Processes,Physicochemical Concepts,Physicochemical Phenomena,Physicochemical Processes,Chemical Phenomenon,Chemical Process,Physical Chemistry Phenomena,Physical Chemistry Process,Physicochemical Phenomenon,Physicochemical Process,Chemical Concept,Chemistry Process, Physical,Chemistry Processes, Physical,Concept, Chemical,Concept, Physical Chemistry,Concept, Physicochemical,Concepts, Chemical,Concepts, Physical Chemistry,Concepts, Physicochemical,Phenomena, Chemical,Phenomena, Physical Chemistry,Phenomena, Physicochemical,Phenomenon, Chemical,Phenomenon, Physicochemical,Physical Chemistry Concept,Physicochemical Concept,Process, Chemical,Process, Physical Chemistry,Process, Physicochemical,Processes, Chemical,Processes, Physical Chemistry,Processes, Physicochemical