DNA-REPAIR CAPACITY CORRELATES WITH MUTAGEN SENSITIVITY IN LYMPHOBLASTOID CELL-LINES

This study describes a correlation between cellular DNA repair capacit y 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 m utagen sensitivity assay, have recently been shown to be useful biomar kers for such susceptibility, Increased in vitro mutagen sensitivity, measured by the number of induced chromatid breaks, has been postulate d 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 e stablished lymphoblastoid cell lines derived from patients with xerode rma pigmentosum (n = 3), ataxia telangiectasia (n = 2), head and neck cancer (n = 3), and melanoma (n 2), and from normal human subjects (It = 6) using UV light, 4-nitroquinoline-1-oxide (4-NQO; an UV-mimetic a gent), and gamma-irradiation as the test agents, The measurements from the HCR assay correlated significantly with the frequency of chromati d breaks induced by either UV irradiation (r = -0.69; P < 0.01) or 4-N QO (I = -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 H CR assay is not suitable to test agents that cause DNA strand breaks, such as gamma-irradiation, whereas the mutagen sensitivity assay is, A lthough reduced cellular DNA repair capacity correlated with increased frequency of mutagen-induced chromatid breaks in these cell lines, th ese two assays have different sensitivities in measuring the repair of damage induced by different carcinogens; therefore, the use of both a ssays is recommended for future molecular epidemiological studies of c ancer susceptibility.