Biomaterial Database

Effect of carcinogenic adducts on transcription by T7 RNA polymerase. 1987

S T Nath, and M S Lee, and L J Romano

The effect of modifying the T7 promoter-containing plasmid pDR100 with aminofluorene (AF), acetylaminofluorene (AAF), and benzo[a]pyrene (B[a]P) adducts on RNA synthesis by the T7 RNA polymerase was determined. We found that increasing levels of each of the three adducts caused a progressive decline in RNA synthesis, but that the inhibition produced by benzo[a]pyrene adducts was substantially greater than that caused by either AF or AAF adducts. Polyacrylamide gel electrophoresis analysis confirmed that the B[a]P adducts more strongly inhibited chain elongation since their presence resulted in the production of RNA fragments having average chain lengths very close to that predicted if each adduct permanently blocked the polymerase during transcription. We have also determined the effect of each type of adduct on the initiation of transcription and show that the T7 RNA polymerase initiates as efficiently on both AF or AAF-containing templates as it does on unmodified DNA, while B[a]P adducts were found to increase in the number of chain starts.

UI	MeSH Term	Description	Entries
D002273	Carcinogens	Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.	Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
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
D005449	Fluorenes	A family of diphenylenemethane derivatives.
D005813	Genes, Synthetic	Biologically functional sequences of DNA chemically synthesized in vitro.	Artificial Genes,Synthetic Genes,Artificial Gene,Gene, Artificial,Gene, Synthetic,Genes, Artificial,Synthetic Gene
D001564	Benzo(a)pyrene	A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.	3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D012321	DNA-Directed RNA Polymerases	Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992).	DNA-Dependent RNA Polymerases,RNA Polymerases,Transcriptases,DNA-Directed RNA Polymerase,RNA Polymerase,Transcriptase,DNA Dependent RNA Polymerases,DNA Directed RNA Polymerase,DNA Directed RNA Polymerases,Polymerase, DNA-Directed RNA,Polymerase, RNA,Polymerases, DNA-Dependent RNA,Polymerases, DNA-Directed RNA,Polymerases, RNA,RNA Polymerase, DNA-Directed,RNA Polymerases, DNA-Dependent,RNA Polymerases, DNA-Directed
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D013604	T-Phages	A series of 7 virulent phages which infect E. coli. The T-even phages T2, T4; (BACTERIOPHAGE T4), and T6, and the phage T5 are called "autonomously virulent" because they cause cessation of all bacterial metabolism on infection. Phages T1, T3; (BACTERIOPHAGE T3), and T7; (BACTERIOPHAGE T7) are called "dependent virulent" because they depend on continued bacterial metabolism during the lytic cycle. The T-even phages contain 5-hydroxymethylcytosine in place of ordinary cytosine in their DNA.	Bacteriophages T,Coliphages T,Phages T,T Phages,T-Phage
D013698	Templates, Genetic	Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.	Genetic Template,Genetic Templates,Template, Genetic
D014158	Transcription, Genetic	The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.	Genetic Transcription