In a human small cell lung carcinoma cell line, GLC4, Adriamycin (ADR) resistance was induced. In the resistant cell line, GLC4/ADR, a 45% decreased intracellular ADR level was found compared to GLC4, but this could not fully explain the resistance. Evaluation of DNA damage in both cell lines after incubation with ADR by alkaline and neutral elution revealed single-strand breaks, DNA-protein cr...

In this review, we focus on the discrepant roles of the DNA repair complex ERCC1/XPF in the prevention of cancer and in the resistance of cancer to chemotherapy. ERCC1/XPF is essential for nucleotide excision repair (NER) incising DNA 5' to the lesion. NER deficiency results in the skin cancer-prone inherited disease xeroderma pigmentosum (XP). The ERCC1/XPF complex is also involved in recombin...

PURPOSE The variable resolution x-ray (VRX) CT scanner provides substantial improvement in the spatial resolution by matching the scanner's field of view (FOV) to the size of the object being imaged. Intercell x-ray cross-talk is one of the most important factors limiting the spatial resolution of the VRX detector. In this work, a new cell arrangement in the VRX detector is suggested to decreas...

The gene-specific formation and repair of interstrand cross-links (ICL) were measured in the dihydrofolate reductase (DHFR) gene in hamster cells. Cells were treated with two different chemotherapeutic agents, nitrogen mustard and cisplatin, and the frequency of cross-links was quantified in the active gene and in a downstream, inactive region. About 5% of total lesions induced by these agents ...

Interstrand DNA-DNA cross-links are highly toxic lesions that are important in medicinal chemistry, toxicology, and endogenous biology. In current models of replication-dependent repair, stalling of a replication fork activates the Fanconi anemia pathway and cross-links are "unhooked" by the action of structure-specific endonucleases such as XPF-ERCC1 that make incisions flanking the cross-link...

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O(6)-methylguanine (MeG), which can eventually become cytotoxic and mu...

A better understanding of the mechanism of chromosomal aberration formation could be obtained by using DNA repair inhibitors. Immortalized normal human (MRC 5 SVI) and ataxia telangiectasia ( AT 5 BIV A ) fibroblastic cell lines were treated with adenosine arabinoside (ara-A) and cytosine arabinoside (ara-C), both potent inhibitors of DNA dsb repair, alone or in combination with x-rays at ...

OBJECTIVE: Little is known about how the biochemical properties of collagen change during tissue regeneration following cartilage damage. In the current study, temporal changes in cartilage repair tissue biochemistry were assessed in a rabbit osteochondral defect. DESIGN: Bilateral full thickness 3mm osteochondral trochlear groove defects were created in 54 adult male skeletally mature New Zea...