DNA Adduct of the Mitomycin C Metabolite 2,7-Diaminomitosene Is a Nontoxic and Nonmutagenic DNA Lesion in Vitro and in Vivo

2005 ◽  
Vol 18 (2) ◽  
pp. 213-223 ◽  
Author(s):  
Christopher D. Utzat ◽  
Cristina C. Clement ◽  
Leilani A. Ramos ◽  
Arunangshu Das ◽  
Maria Tomasz ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Dna Adduct ◽  
Dna Lesion

N-(2-hydroxyethyl)-N-[2-(7-guaninyl)ethyl]amine, the putative major DNA adduct of cyclophosphamide in vitro and in vivo in the rat

1988 ◽  
Vol 37 (15) ◽  
pp. 2979-2985 ◽  
Author(s):  
Alistair J. Benson ◽  
Carl N. Martin ◽  
R.Colin Garner
Keyword(s):  
Dna Adduct ◽  
Ethyl Amine

scholarly journals MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas

2020 ◽  
Author(s):  
Barbara Oldrini ◽  
Nuria Vaquero-Siguero ◽  
Quanhua Mu ◽  
Paula Kroon ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Chemotherapy Resistance ◽  
Glioma Cells ◽  
Promoter Hypermethylation ◽  
Dna Adduct ◽  
Genomic Rearrangements ◽  
Low Grade ◽  
Methylguanine Dna Methyltransferase

AbstractTemozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carries MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that the MGMT genomic rearrangements contribute to TMZ resistance both in vitro and in vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.

scholarly journals RNA polymerase bypass at sites of dihydrouracil: implications for transcriptional mutagenesis.

1995 ◽  
Vol 15 (12) ◽  
pp. 6729-6735 ◽  
Author(s):  
J Liu ◽  
W Zhou ◽  
P W Doetsch
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerases ◽  
Dna Damages ◽  
Mutant Proteins ◽  
Dna Lesion ◽  
Transcriptional Mutagenesis ◽  
Rapid Generation ◽  
Transition Mutation

Dihydrouracil (DHU) is a major base damage product formed from cytosine following exposure of DNA to ionizing radiation under anoxic conditions. To gain insight into the DNA lesion structural requirements for RNA polymerase arrest or bypass at various DNA damages located on the transcribed strand during elongation, DHU was placed onto promoter-containing DNA templates 20 nucleotides downstream from the transcription start site. In vitro, single-round transcription experiments carried out with SP6 and T7 RNA polymerases revealed that following a brief pause at the DHU site, both enzymes efficiently bypass this lesion with subsequent rapid generation of full-length runoff transcripts. Direct sequence analysis of these transcripts indicated that both RNA polymerases insert primarily adenine opposite to the DHU site, resulting in a G-to-A transition mutation in the lesion bypass product. Such bypass and insertion events at DHU sites (or other types of DNA damages), if they occur in vivo, have a number of important implications for both the repair of such lesions and the DNA damage-induced production of mutant proteins at the level of transcription (transcriptional mutagenesis).

Autoradiographic study of chick limb cartilage in vivo and in vitro and its response to mitomycin C (MMC)

1975 ◽  
Vol 93 (3) ◽  
pp. 440-446 ◽  
Author(s):  
Shamer Singh ◽  
D.N. Sinha ◽  
G.C. Prasad
Keyword(s):  
Mitomycin C ◽  
Autoradiographic Study

scholarly journals In Vivo Titration of Mitomycin C Action by Four Escherichia coli Genomic Regions on Multicopy Plasmids

2001 ◽  
Vol 183 (7) ◽  
pp. 2259-2264 ◽  
Author(s):  
Yan Wei ◽  
Amy C. Vollmer ◽  
Robert A. LaRossa
Keyword(s):  
Escherichia Coli ◽  
Mitomycin C ◽  
Transcriptional Activation ◽  
Efflux Pump ◽  
Wild Type ◽  
Potent Inducer ◽  
E Coli ◽  
Genomic Regions

ABSTRACT Mitomycin C (MMC), a DNA-damaging agent, is a potent inducer of the bacterial SOS response; surprisingly, it has not been used to select resistant mutants from wild-type Escherichia coli. MMC resistance is caused by the presence of any of four distinctE. coli genes (mdfA, gyrl, rob, andsdiA) on high-copy-number vectors. mdfAencodes a membrane efflux pump whose overexpression results in broad-spectrum chemical resistance. The gyrI (also called sbmC) gene product inhibits DNA gyrase activity in vitro, while the rob protein appears to function in transcriptional activation of efflux pumps. SdiA is a transcriptional activator of ftsQAZ genes involved in cell division.

DNA adduct formation by O-phenylphenol metabolite in vivo and in vitro

1992 ◽  
Vol 13 (8) ◽  
pp. 1469-1473 ◽  
Author(s):  
Keiko Ushiyama ◽  
Fumiko Nagai ◽  
Atsuko Nakagawa ◽  
Itsu Kano
Keyword(s):  
Adduct Formation ◽  
Dna Adduct
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