Peroxynitrite-induced mutation spectra of pSP189 following replication in bacteria and in human cells

Juedes, Marlene J.; Wogan, Gerald N.

doi:10.1016/0027-5107(95)00152-2

Cited by 185 publications

(148 citation statements)

References 35 publications

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“…The spontaneous mutation frequency of the pSP189 shuttle vector plasmid replicated in A549 cells was very low in this study. Only six spontaneous mutants were obtained from a total of 29,324 colonies screened, giving a mutation frequency of 2.04 × 10 −4 , which is consistent with previous reports [25][26][27]. In contrast, TCHQ treatment produced 41 plasmid mutations in 10,498 colonies, which gave a calculated mutation frequency of 39.06 × 10 −4 .…”

Section: High Frequency Of Tchq-induced Mutations In Psp189supporting

confidence: 88%

“…However, from the detection of TCHQ-DNA adducts, we hypothesize that TCHQ may react with plasmid DNA to form TCHQ-DNA adducts, and G:C base pairs are the preferential source for generating these TCHQ-DNA adducts. TCHQ-DNA adducts may pair with T, G or protonated adenine, in addition to C [25,26,31]. However, the levels of AP sites and 8-OH-dG were estimated to be approximately two orders of magnitude greater than the previously reported levels from direct DNA adducts [37].…”

Section: Discussionmentioning

confidence: 73%

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Characterization of TCHQ-induced genotoxicity and mutagenesis using the pSP189 shuttle vector in mammalian cells

Wang

Jiao

et al. 2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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a b s t r a c tTetrachlorohydroquinone (TCHQ) is a major toxic metabolite of the widely used wood preservative, pentachlorophenol (PCP), and it has also been implicated in PCP genotoxicity. However, the underlying mechanisms of genotoxicity and mutagenesis induced by TCHQ remain unclear. In this study, we examined the genotoxicity of TCHQ by using comet assays to detect DNA breakage and formation of TCHQ-DNA adducts. Then, we further verified the levels of mutagenesis by using the pSP189 shuttle vector in A549 human lung carcinoma cells. We demonstrated that TCHQ causes significant genotoxicity by inducing DNA breakage and forming DNA adducts. Additionally, DNA sequence analysis of the TCHQ-induced mutations revealed that 85.36% were single base substitutions, 9.76% were single base insertions, and 4.88% were large fragment deletions. More than 80% of the base substitutions occurred at G:C base pairs, and the mutations were G:C to C:G, G:C to T:A or G:C to A:T transversions and transitions. The most common types of mutations in A549 cells were G:C to A:T (37.14%) and A:T to C:G transitions (14.29%) and G:C to C:G (34.29%) and G:C to T:A (11.43%) transversions. We identified hotspots at nucleotides 129, 141, and 155 in the supF gene of plasmid pSP189. These mutation hotspots accounted for 63% of all single base substitutions. We conclude that TCHQ induces sequence-specific DNA mutations at high frequencies. Therefore, the safety of using this product would be carefully examined.

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Section: High Frequency Of Tchq-induced Mutations In Psp189supporting

confidence: 88%

Section: Discussionmentioning

confidence: 73%

Characterization of TCHQ-induced genotoxicity and mutagenesis using the pSP189 shuttle vector in mammalian cells

Wang

Jiao

et al. 2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…• and superoxide, also induced pSP189 supF mutations, predominantly G:C to T:A (10,15). G:C to T:A mutations occurred in the supF gene of pSP189 replicating in AD293 cells co-cultivated with activated macrophages (18).…”

Section: Proportion Of Mutants (mentioning

confidence: 92%

“…•- (10,15,18) and NO • gas (42), suggesting that NO • may be a major contributor to the observed mutagenesis.…”

Section: Proportion Of Mutants (mentioning

confidence: 96%

Intracellular and extracellular factors influencing the genotoxicity of nitric oxide and reactive oxygen species

Kim

2017

Oncology Letters

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Abstract. A number of factors affect cellular responses to nitric oxide (NO • ) and reactive oxygen species (ROS), including their source, concentration, cumulative dose, target gene and biological milieu. This limits the extrapolation of data to in vivo pathological states in which NO• and ROS may be important. The present study investigated lethality and mutagenesis in the HPRT and TK1 genes of human lymphoblastoid TK6 cells exposed to NO• and ROS derived from two delivery methods: A reactor system and a Transwell™ co-culture. The delivery of NO• into the medium at controlled steady-state concentrations (given in µM/min) and the production of NO• and ROS by activated macrophages, resulted in a time-dependent decrease in total cell numbers, and an increase in mutation frequency (MF), compared with untreated controls. This increase in MF was effectively suppressed by N-methyl-L-arginine monoacetate. Single base substitutions were the most common type of spontaneous and NO• induced mutations in HPRT, followed by exon exclusions and small deletions in both delivery systems. Among the single base pair substitutions, an equal frequency of four types of single base substitutions were identified in TK6 cells exposed to NO• delivered by the reactor system, whereas G:C to T:A transversions and A:T to G:C transitions were more frequent in the co-culture system. Taken together, these results demonstrate that both the delivery method of NO • and ROS, and the target genes are determinants of observed cytotoxic and mutagenic responses, indicating that these parameters need to be considered in assessing the potential effects of NO• and ROS in vivo.

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“…Therefore, 8-nitroguanine is a potentially mutagenic DNA lesion, which may contribute to inflammation-related carcinogenesis. In the ONOO --treated supF shuttle vector plasmid, which was then replicated in Escherichia coli, the majority of mutations occurred at G:C base pairs, predominantly involving G → T transversions (Juedes & Wogan, 1996; M.Y. .…”

Section: Dna Damage Mediated By Reactive Species Under Inflammatory Cmentioning

confidence: 99%

Role of Chronic Inflammation and Resulting DNA Damage in Cervical Carcinogenesis Induced by Human Papillomavirus

Hiraku¹

2012

Human Papillomavirus and Related Diseases - From Bench to Bedside - Research Aspects

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Peroxynitrite-induced mutation spectra of pSP189 following replication in bacteria and in human cells

Cited by 185 publications

References 35 publications

Characterization of TCHQ-induced genotoxicity and mutagenesis using the pSP189 shuttle vector in mammalian cells

Characterization of TCHQ-induced genotoxicity and mutagenesis using the pSP189 shuttle vector in mammalian cells

Intracellular and extracellular factors influencing the genotoxicity of nitric oxide and reactive oxygen species

Role of Chronic Inflammation and Resulting DNA Damage in Cervical Carcinogenesis Induced by Human Papillomavirus

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