DNA repair in lymphoblastoid cell lines from patients with head and neck cancer.
OBJECTIVE: To analyze and compare components of the 3 primary DNA repair pathways of Epstein-Barr virus-transformed 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 carcinogen-damaged 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 transcriptase-polymerase 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 and hPMS1) 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 of XRCC4 (P = .01) 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.
Sturgis, EM; Clayman, GL; Guan, Y; Guo, Z; Wei, Q
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