Stannous chloride (SnCl(2)) and UVA induce DNA lesions through ROS. The aim of this work was to study the toxicity induced by UVA preillumination, followed by SnCl(2) treatment. E. coli BER mutants were used to identify genes which could play a role in DNA lesion repair generated by these agents. The survival assays showed (i) The nfo mutant was the most sensitive to SnCl(2); (ii) lethal synerg...

The y-ray sensitivity of skin fibroblasts from six members of a cancer family was investigated using a colony-forming assay. Fibroblasts from the three members with cancer (two sisters with acute myelogenous leukemia and the mother with cervical carcinoma) showed a significant (p < 0.05) increase in radiosensitivity, while three members without cancer (the father and two sons) showed a normal r...

We have studied the effects of 2-deoxy-D-Glucose (2-DG) on the recovery of potentially lethal damage (PLDR), repair of chromosomal DNA, cyclobutane pyrimidine dimers (CPDs), reverse mutation and gene-conversion in UVC (254 nm) irradiated yeast. As studied by pulsed-field gel electrophoresis, post-irradiation chromosomal DNA repair kinetics in a phosphate buffer (PB) with 10 mM glucose (G) was b...

DNA double strand breaks (DSBs) are abrasions caused in both strands of the DNA duplex following exposure to both exogenous and endogenous conditions. Such abrasions have deleterious effect in cells leading to genome rearrangements and cell death. A number of repair systems including homologous recombination (HR) and non-homologous end-joining (NHEJ) have been evolved to minimize the fatal effe...

To obtain an overall picture of the repair of DNA single and double strand breaks in a defined region of chromatin in vivo, we studied their repair in a ~170 kb circular minichromosome whose length and topology are analogous to those of the closed loops in genomic chromatin. The rate of repair of single strand breaks in cells irradiated with γ photons was quantitated by determining the sensitiv...

Epidermal growth factor receptor (EGFR) overexpression is associated with resistance to chemotherapy and radiotherapy. It modulates DNA repair after radiation-induced damage through association with the catalytic subunit of DNA protein kinase (DNA-PKcs). We investigated the role of EGFR nuclear import and its association with DNA-PKcs on DNA repair after exposure to cisplatin or ionizing radiat...

Trichothiodystrophy (TTD) is a rare autosomal premature-ageing and neuroectodermal disease. The photohypersensitive form of TTD is caused by inherited mutations in three of the 10 subunits of the basal transcription factor TFIIH. TFIIH is an essential transcription initiation factor that is also pivotal for nucleotide excision repair (NER). Photosensitive TTD is explained by deficient NER, dedi...

Replication of the oxidative lesion 8-oxo-7,8-dihydroguanine (GO) leads to the formation of both 8-oxo-7,8-dihydroguanine:adenine (GO:A) and 8-oxo-7,8-di-hydroguanine:cytosine (GO:C) pairs. The repair and mutagenic potency of these two kinds of base pairs were studied in simian COS7 and human MRC5V1 cells using the shuttle vector technology. Shuttle vectors carrying a unique GO residue opposite...

Recent evidence has linked cellular DNA repair capacity to the chemosensitivity of cancer cells to alkylating agents. Using single-cell gel electrophoresis ("comet assay"), we have analyzed the induction and differential processing of DNA damage in human lymphocytes derived from healthy donors and from patients with chronic lymphatic leukemia (CLL) after exposure to N-ethyl-N-nitrosourea in vit...

We have sought to clarify the potential activity of the S-phase-specific antileukemic agent 1-beta-D-arabinofuranosylcytosine (ara-C), an inhibitor of DNA synthesis, in quiescent cells that are substantially non-sensitive to nucleoside analogues. It was hypothesized that the combination of ara-C with DNA damaging agents that initiate DNA repair will expand ara-C cytotoxicity to non-cycling cell...