Shimoi K, Kawabata H, Tomita I
Laboratory of Health Science, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Mutat Res. 1992 Aug;268(2):287-95. doi: 10.1016/0027-5107(92)90234-s.
Most heterocyclic amines and beta-carbolines--harman, norharman, harmine, harmaline--enhanced UVC (254 nm) induced mutagenesis without microsomal activation in E. coli B/r WP2. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was most effective and increased UVAB (295-400 nm) induced mutations as well as UVC induced ones. Trp-P-1 enhanced the frequencies of mutations induced by not only UV but also 4-nitroquinoline-1-oxide (4NQO) or 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF2), while it showed little effect on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or gamma-ray induced mutagenesis. Trp-P-1 decreased the survival of UVC irradiated cells of CM571recA. However, these effects of Trp-P-1 on UVC induced mutagenesis and lethality were not observed in WP2suvrA which is excision repair deficient. The alkaline sucrose gradient sedimentation analysis demonstrated that Trp-P-1 blocked the incision step in DNA excision repair. Further, pretreatment with Trp-P-1 before UVC irradiation showed no effect on UVC induced mutagenesis. Similar effects were also seen in the case of harman or norharman. These results suggest that heterocyclic amines and beta-carbolines inhibit DNA excision repair directly or indirectly, thus enhancing UV or chemically induced mutagenesis.
大多数杂环胺和β-咔啉——哈尔满、去甲哈尔满、哈尔明碱、去氢骆驼蓬碱——在大肠杆菌B/r WP2中能增强紫外线C（254纳米）诱导的诱变作用，且无需微粒体激活。3-氨基-1,4-二甲基-5H-吡啶并[4,3-b]吲哚（Trp-P-1）最为有效，它能增加紫外线A/B（295 - 400纳米）诱导的突变以及紫外线C诱导的突变。Trp-P-1不仅能提高紫外线诱导的突变频率，还能提高4-硝基喹啉-1-氧化物（4NQO）或2-（2-呋喃基）-3-（5-硝基-2-呋喃基）丙烯酰胺（AF2）诱导的突变频率，而对N-甲基-N'-硝基-N-亚硝基胍（MNNG）或γ射线诱导的诱变作用影响很小。Trp-P-1降低了CM571recA的紫外线C照射细胞的存活率。然而，在切除修复缺陷的WP2suvrA中未观察到Trp-P-1对紫外线C诱导的诱变作用和致死率的这些影响。碱性蔗糖梯度沉降分析表明，Trp-P-1阻断了DNA切除修复中的切口步骤。此外，在紫外线C照射前用Trp-P-1预处理对紫外线C诱导的诱变作用没有影响。哈尔满或去甲哈尔满的情况也观察到了类似的效果。这些结果表明，杂环胺和β-咔啉直接或间接抑制DNA切除修复，从而增强紫外线或化学诱导的诱变作用。
