Carcinogenesis is known to be a multislep process which involves two 01' m(Jn.~ events C<lt1 result from point mutations, chromosomal rearmngements (Cr<Jcc amI Klein 1990), inscrtions or dcletions of genes, and gene amplification. Cell replicmiof} is required to cOßvert DNA damage to mutations, irrespective ofwhether this dmnagt: is occurring sp<.mtaneous1y 01' induced by DNA damaging (genotoxi...

To investigate how the nucleotide excision repair initiator XPC locates DNA damage in mammalian cell nuclei we analyzed the dynamics of GFP-tagged XPC. Photobleaching experiments showed that XPC constantly associates with and dissociates from chromatin in the absence of DNA damage. DNA-damaging agents retard the mobility of XPC, and UV damage has the most pronounced effect on the mobility of XP...

Modifications to the alkaline Comet assay by using lesion-specific endonucleases, such as formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (ENDOIII, also known as Nth), can detect DNA bases with oxidative damage. This modified assay can be used to assess the genotoxic/carcinogenic potential of environmental chemicals. The goal of this study was to validate the ability of this modi...

Poly-ADP-ribosylation is a post-translational modification generated in high amounts by poly-ADP-ribose polymerases (PARPs) in response to cellular stress, especially genotoxic stimuli. DNA damage-induced PARylation significantly changes local chromatin structure and triggers the accumulation of several DNA damage response (DDR) proteins at the DNA lesions. In this review, we will discuss the r...

DNA damage occurs via endogenous and exogenous genotoxic agents and compromises a genome's integrity. Knowing where damage occurs within a genome is crucial to understanding the repair mechanisms which protect this integrity. This paper describes a new development based on microarray technology which uses ultraviolet light induced DNA damage as a paradigm to determine the position and frequency...

The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and ski...

Background: Natural products are characterized by a complex chemical composition and capable of concurrently modulate several signalling pathways. Considering the biological complexity carcinogenesis, natural represent key components therapeutic armamentarium for oncological diseases. The bark Terminalia arjuna is used in traditional Ayurvedic medicine its astringent, expectorant, cardiotonic, ...

This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorop...

Apurinic/apyrimidinic endonuclease 1 (APE1) is the main abasic endonuclease in the base excision repair (BER) pathway of DNA lesions caused by oxidation/alkylation in mammalian cells; within nucleoli it interacts with nucleophosmin and rRNA through N-terminal Lys residues, some of which (K(27)/K(31)/K(32)/K(35)) may undergo acetylation in vivo. Here we study the functional role of these modific...

Calypso (thiacloprid), Poncho (clothianidin), Gaucho (imidacloprid), and Jade (imidacloprid) are commercial neonicotinoid insecticides, a new class of agrochemicals in México. However, genotoxic and cytotoxic studies have not been performed. In the present study, human peripheral blood lymphocytes (PBL) were exposed in vitro to different concentrations of the four insecticides. The genotoxic an...