Boesen J J, Stuivenberg S, Thyssens C H, Panneman H, Darroudi F, Lohman P H, Simons J W
MGC-Department of Radiation Genetics and Chemical Mutagenesis, University of Leiden, The Netherlands.
Mol Gen Genet. 1992 Aug;234(2):217-27. doi: 10.1007/BF00283842.
Cells of the mouse T-lymphoma line GRSL13 were treated with 8-methoxy-psoralen plus longwave ultraviolet light (PUVA) under conditions where the biological effects are mainly due to non-persistent DNA cross-links (PUVA-CL treatment). Fluctuation analysis showed that PUVA-CL treatment resulted in an enhancement of the mutation rate in the progeny of treated cells, which persisted until the eleventh generation after treatment. Since only 5 cross-links are available to account for 52 mutational events observed in the coding region, about 90% of the induced mutational events must have been untargeted. This was confirmed by molecular analysis of these mutations, which showed that 53% of the point mutations arose at sites which are not a target for psoralens. This supports the hypothesis that stress responses may give rise to untargeted mutagenesis. Further support for this hypothesis is provided by the observation that 8-methoxy-psoralen (8-MOP) or UVA alone (both of which are known to induce many pleiotropic effects) each acted as indirect mutagen by enhancing the mutation rate 2-4 fold in the progeny of treated cells.
在生物效应主要归因于非持久性DNA交联的条件下（PUVA-CL处理），用8-甲氧基补骨脂素加长波紫外线（PUVA）处理小鼠T淋巴瘤细胞系GRSL13的细胞。波动分析表明，PUVA-CL处理导致处理后细胞后代的突变率增加，这种增加一直持续到处理后的第十一代。由于仅有5个交联可解释在编码区观察到的52个突变事件，因此约90%的诱导突变事件必定是非靶向性的。对这些突变的分子分析证实了这一点，该分析表明53%的点突变出现在补骨脂素并非靶向的位点。这支持了应激反应可能导致非靶向诱变的假说。8-甲氧基补骨脂素（8-MOP）或单独的UVA（两者均已知可诱导多种多效性效应）各自通过使处理后细胞后代的突变率提高2至4倍而作为间接诱变剂，这一观察结果为该假说提供了进一步支持。
