Direct comparison, in human resting lymphocytes, of the inter-individual variations in unscheduled DNA synthesis induced by N-acetoxy-2-acetylaminofluorene and ultraviolet irradiation

Abstract

• Unscheduled DNA synthesis (UDS) in human leukocytes has become a popular tool for estimating an individual's DNA-repair capacity and sensitivity to mutagens. The physical induction of UDS by UV-irradiation, as opposed to the chemical induction of UDS by N-acetoxy-2-acetylaminofluorene (NA-AAF), has yielded contradictory reports in the literature regarding inter-individual variations relating to risk factors such as age. In an effort to resolve this anomaly, we have compared directly, in duplicate lymphocyte samples from 29 male individuals, the UDS induced by 10 μM NA-AAF and UV-irradiation of 10 J·m −2. The kinetics of UV-induced UDS was very “fast”, being 50% complete within 2.5 h whereas the corresponding value for NA-AAF-induced UDS was 7 h. Consistent with our previous studies, individual variations in NA-AAF-induced UDS were positively correlated to age. However, a strong tendency toward both positive and negative correlations to an individual's age could be calculated depending on whether ◀fast”- or “slow”-UV-induced DNA repair was taken into consideration. • These data, therefore, question the validity of previous reports establishing DNA-repair deficiencies when UV-induced UDS was used for quantitation and the “fast” UV repair was only partially estimated because of early delays in the 3H-dThd pulse. If appropriately pulsed with 3H-dThd, then the inter-individual fluctuations in NA-AAF- and UV-induced UDS correlated to each other in a highly significant linear manner ( r = 0.51, p < 0.01). Basic similarities between NA-AAF- and UV-induced UDS were also observed when both parameters correlated to the phytohemagglutinin responsiveness of the lymphocytes. • A working hypothesis, based on environmentally influenced changes in chromatin structure regulating the relative accessibility of NA-AAF- and UV-induced lesions for repair, was formulated to explain the parallel inter-individual fluctuations of NA-AAF- and UV-induced UDS.