DNA repair capacity correlates with mutagen sensitivity in lymphoblastoid cell lines.
This study describes a correlation between cellular DNA repair capacity and the frequency of mutagen-induced in vitro chromosomal breaks in selected lymphoblastoid cell lines. Two assays, host cell reactivation (HCR) assay for measuring cellular DNA repair capacity and in vitro mutagen sensitivity assay, have recently been shown to be useful biomarkers for such susceptibility. Increased in vitro mutagen sensitivity, measured by the number of induced chromatid breaks, has been postulated to reflect decreased capacity of DNA repair, as measured by the HCR assay. However, these two assays have not been examined in parallel to test this hypothesis. In this study, we performed both assays in 16 established lymphoblastoid cell lines derived from patients with xeroderma pigmentosum (n = 3), ataxia telangiectasia (n = 2), head and neck cancer (n = 3), and melanoma (n = 2), and from normal human subjects (n = 6) using UV light, 4-nitroquinoline-1-oxide (4-NQO; an UV-mimetic agent), and gamma-irradiation as the test agents. The measurements from the HCR assay correlated significantly with the frequency of chromatid breaks induced by either UV irradiation (r = -0.69; P < 0.01) or 4-NQO (r = -0.70; P < 0.01). Although published data suggest that damage induced by UV and 4-NQO may be repaired by different pathways, the two agents induced similar frequencies of chromatid breaks (r = 0.68; P < 0.01) in the tested cell lines. Our results also indicated that the HCR assay is not suitable to test agents that cause DNA strand breaks, such as gamma-irradiation, whereas the mutagen sensitivity assay is. Although reduced cellular DNA repair capacity correlated with increased frequency of mutagen-induced chromatid breaks in these cell lines, these two assays have different sensitivities in measuring the repair of damage induced by different carcinogens; therefore, the use of both assays is recommended for future molecular epidemiological studies of cancer susceptibility.
Wei
Q
Q
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Spitz
M R
MR
Gu
J
J
Cheng
L
L
Xu
X
X
Strom
S S
SS
Kripke
M L
ML
Hsu
T C
TC
D015112:4-Nitroquinoline-1-oxide / Q000009:adverse effects; D001260:Ataxia Telangiectasia / Q000473:pathology; D015415:Biomarkers; D002273:Carcinogens / Q000009:adverse effects; D002460:Cell Line; D002842:Chromatids / Q000187:drug effects / Q000528:radiation effects; D019457:Chromosome Breakage; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004198:Disease Susceptibility; D005720:Gamma Rays / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000473:pathology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008545:Melanoma / Q000473:pathology; D009153:Mutagens / Q000009:adverse effects*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays / Q000009:adverse effects; D014983:Xeroderma Pigmentosum / Q000473:pathology
D015415:Biomarkers; D002273:Carcinogens; D009153:Mutagens; D015112:4-Nitroquinoline-1-oxide; D004247:DNA