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DNA Repair in Lymphoblastoid Cell Lines From Patients With Head and Neck Cancer
Erich M. Sturgis, MD;
Gary L. Clayman, DDS, MD;
Yongli Guan, BA;
Zhaozheng Guo, MD;
Qingyi Wei, MD, PhD
Arch Otolaryngol Head Neck Surg. 1999;125:185-190.
Objective To analyze and compare components of the 3 primary DNA repair pathways of Epstein-Barr virustransformed lymphocyte (lymphoblastoid) cell lines derived from 9 patients with squamous cell carcinoma of the head and neck and 11 cancer-free controls. These cell lines were previously characterized by using an established cytogenetic marker of cancer susceptibility (mutagen sensitivity assay).
Design To evaluate nucleotide excision repair (NER), we measured the reactivation level of a tobacco carcinogendamaged plasmid containing a bacterial reporter gene transfected into these cells. To assess mismatch repair (MMR) and recombinational repair, selected gene transcript levels were quantified by using a multiplex reverse transcriptasepolymerase chain reaction assay. The results of these DNA repair assays were correlated with the previously measured mutagen sensitivity values.
Results The NER capacities of the 2 groups were similar: 25.1% (range, 14.3%-33.3%) for the patient cell lines and 26.0% (range, 9.4%-47.7%) for the control lines. Transcriptase levels for 6 MMR genes (hMSH3, hMSH2, hPMS2, GTBP, hMLH1, andhPMS1) did not differ in the 2 groups. Transcript levels for 4 of 6 recombinational repair genes (XRCC7, XRCC6, XRCC1, and RAD51) were higher in the patient cell lines, though this difference was significant only for XRCC7 (P = .003). The mutagen sensitivity values correlated with the NER capacity (P = .05) and the expression ofXRCC4 (P = .0l) and RAD51 (P = .06) genes.
Conclusions As revealed by the above-named assays, these lymphoblastoid cell lines derived from patients with head and neck cancer had minor alterations in DNA repair function. However, these differences in DNA repair do appear to affect the cytogenetic marker of cancer susceptibility, mutagen sensitivity.
From the Departments of Head and Neck Surgery (Drs Sturgis and Clayman) and Epidemiology (Ms Guan and Drs Guo and Wei), the University of Texas, M. D. Anderson Cancer Center, Houston.
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