Search results for "pig"

Antitumor Effects of a Combined 5-Aza-2′Deoxycytidine and Valproic Acid Treatment on Rhabdomyosarcoma and Medulloblastoma in Ptch Mutant Mice

2009

Abstract Patched (Ptch) heterozygous mice develop medulloblastoma (MB) and rhabdomyosarcoma (RMS) resembling the corresponding human tumors. We have previously shown that epigenetic silencing of the intact Ptch allele contributes to tumor formation in this model. Here, we investigated whether targeting of epigenetic silencing mechanisms could be useful in the treatment of Ptch-associated cancers. A reduction of endogenous DNA methyltransferase1 (Dnmt1) activity significantly reduced tumor incidence in heterozygous Ptch knockout mice. A combined treatment with the Dnmt inhibitor 5-aza-2′deoxycytidine (5-aza-dC) and the histone deacetlyase (HDAC) inhibitor valproic acid (VPA) efficiently prev…

Nucleotide excision repair of abasic DNA lesions

2019

AbstractApurinic/apyrimidinic (AP) sites are a class of highly mutagenic and toxic DNA lesions arising in the genome from a number of exogenous and endogenous sources. Repair of AP lesions takes place predominantly by the base excision pathway (BER). However, among chemically heterogeneous AP lesions formed in DNA, some are resistant to the endonuclease APE1 and thus refractory to BER. Here, we employed two types of reporter constructs accommodating synthetic APE1-resistant AP lesions to investigate the auxiliary repair mechanisms in human cells. By combined analyses of recovery of the transcription rate and suppression of transcriptional mutagenesis at specifically positioned AP lesions, w…

Role of Endogenous Oxidative DNA Damage in Carcinogenesis: What Can We Learn from Repair-Deficient Mice?

2002

Basal steady-state levels of oxidative DNA base modifications such as 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG) are observed in all types of cells, most probably due to a continuous generation of reactive oxygen species (ROS) in the cellular oxygen metabolism, and it has long been suspected that they might play an important role in the initiation of carcinogenesis. Experimental evidence for this assumption can be obtained by studying the effects of a modulation of the steady-state levels, either by in- or decreasing the generation of oxidative DNA damage, on spontaneous mutation rates and cancer incidence. However, clear answers have not yet been obtained by these strategies. It is still…

Influences of histone deacetylase inhibitors and resveratrol on DNA repair and chromatin compaction

2013

Accessibility of DNA is a prerequisite for both DNA damage and repair. Therefore, the chromatin structure is expected to have major impact on both processes, with opposite consequences for the stability of the genome. To analyse the influence of chromatin compaction on the generation and repair of various types of DNA modifications, we modulated the global chromatin structure of AS52 Chinese hamster ovary cells and HeLa cells by treatment with either histone deacetylase inhibitors or resveratrol and measured the repair kinetics of (i) pyrimidine dimers induced by ultraviolet B, (ii) oxidised purines generated by photosensitisation and (iii) single-strand breaks induced by H2O2, using an alk…

Heterochromatin Networks: Topology, Dynamics, and Function (a Working Hypothesis)

2021

Open systems can only exist by self-organization as pulsing structures exchanging matter and energy with the outer world. This review is an attempt to reveal the organizational principles of the heterochromatin supra-intra-chromosomal network in terms of nonlinear thermodynamics. The accessibility of the linear information of the genetic code is regulated by constitutive heterochromatin (CHR) creating the positional information in a system of coordinates. These features include scale-free splitting-fusing of CHR with the boundary constraints of the nucleolus and nuclear envelope. The analysis of both the literature and our own data suggests a radial-concentric network as the main structural…

Histone carbonylation occurs in proliferating cells

2012

12 páginas, 10 figuras (que no es encuentran en este documento, se pueden ver en: http://www.sciencedirect.com/science/article/pii/S0891584912000664)

Effect of Ultraviolet Irradiation on Biosynthesis of Dna in Guinea-Pig Skin in Vivo

1974

The molecular and metabolic alterations preceding the clinical manifestation of a photobiologic process, the erythematous or sunburn reaction, were investigated in mammalian skin in vivo. The effect of a moderate (2.5–3 times the minimal erythema dose [MED]) and a large (6–8 times MED) dose of ultraviolet radiation (290–320 nm) on the incorporation of [ Me - 3 H]-thymidine into epidermal cell DNA of guinea pigs was studied. The epilated half of the back of each animal was irradiated with various doses of ultraviolet light, and the other half served as the nonirradiated control. The amount of intraperitoneally injected [ Me - 3 H]-thymidine incorporated into the DNA was determined by the iso…

Asynchronous replication dynamics of imprinted and non-imprinted chromosome regions in early mouse embryos.

2008

We have used interphase FISH to analyze the replication behavior of four imprinted chromosome regions (Snrpn, Zim1-Peg3, Dlk1-Gtl2, and Igf2r) and five non-imprinted regions in mouse one-cell to morula-stage embryos and embryonic fibroblasts. In general, imprinted chromosome regions showed the expected asynchronous pattern of replication throughout all analyzed stages of preimplantation development and in differentiated cells. The Dlk1-Gtl2 locus which is not expressed and Igf2r which is biallelically expressed in early embryos showed a relaxation of replication asynchrony at the morula stage. Asynchronous replication in zygotes and two-cell embryos was not specific to imprinted regions. Th…

The DNA cytosine methylome of Streptomyces coelicolor

2019

Oxidatively generated DNA base modifications: Relation to eustress and distress

2020

Abstract Oxidative stress at the DNA, i.e., the generation of DNA damage by endogenously produced reactive oxygen species, is of particular concern as it can give rise to mutations and thereby an increased cancer risk. On the other hand, there is accumulating evidence that oxidized DNA bases, in particular 8-oxo-7,8-dihydroguanine (8-oxoG), are actively generated in mammalian cells as epigenetic marks and are involved in transcriptional regulation. To better understand this apparent paradox, this chapter first describes the types and mechanisms of DNA damage under conditions of exogenous and endogenous oxidative stress. It then summarizes the indications that oxidatively generated DNA damag…