Susceptibility of proliferating cells to benzo[a]pyrene-induced homologous recombination in mice
Susceptibility of proliferating cells to benzo[a]pyrene-induced homologous recombination in mice
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DOI：
10.1093/carcin/22.4.641
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发表时间：
2001-04-01
期刊：
影响因子：
4.7
通讯作者：
Schiestl, RH
中科院分区：
文献类型：
--
作者：
Bishop, AJR;Kosaras, B;Schiestl, RH
红眼不稳定突变p（un）是小鼠红眼p基因内70 kb串联重复的结果。通过同源缺失/重组，重复区域的一个拷贝的缺失在胚胎中自发发生，并导致皮毛和眼睛中的色素斑。这样的缺失事件是可诱导的各种DNA损伤剂，因为我们已经观察到的毛皮和眼睛斑点检测。在这里，我们描述了一项研究的影响，暴露于苯并[a]芘（B[a]P）在不同的时间发展的逆转诱导的眼睛。在此之前，我们已经报道了视网膜色素上皮（RPE）在粉红色眼睛不稳定的逆转模式中显示出位置效应杂色表型。在妊娠第十天急性暴露于B[a]P或X射线后，在成人RPE的一个独特区域中检测到逆转事件的频率增加，在眼睛发育的不同时间检查暴露揭示了B[a]P和X射线都导致回复事件的频率增加，尽管这种增加仅在B[a]P暴露后才显着，类似于我们之前的报告，仅限于妊娠第10天的接触。在本研究中，对B[a] P暴露的RPE的检查揭示了诱导事件所在的不同区域，并且发现这些区域的位置与视神经的距离随着暴露时间的推移而增加。这种位置效应直接反映了先前观察到的RPE的发育模式，即离视神经最远的区域中的细胞增殖最活跃。显示转化（色素）表型的RPE细胞的数量和位置强烈支持分裂细胞对致癌物诱导的缺失风险最高的建议。
The pink-eyed unstable mutation, p(un), is the result of a 70 kb tandem duplication within the murine pink-eyed, p, gene, Deletion of one copy of the duplicated region by homologous deletion/recombination occurs spontaneously in embryos and results in pigmented spots in the fur and eye. Such deletion events are inducible by a variety of DNA damaging agents, as we have observed previously with both fur- and eye-spot assays. Here we describe a study of the effect of exposure to benzo[a]pyrene (B[a]P) at different times of development on reversion induction in the eye. Previously we, among others, have reported that the retinal pigment epithelium (RPE) displays a position effect variegation phenotype in the pattern of pink-eyed unstable reversions, Following an acute exposure to B[a]P or X-rays on the tenth day of gestation an increased frequency of reversion events was detected in a distinct region of the adult RPE, Examining exposure at different times of eye development reveals that both B[a]P and X-rays result in an increased frequency of reversion events, though the increase was only significant following B[a]P exposure, similar to our previous report limited to exposure on the tenth day of gestation. Examination of B[a]P-exposed RPE in the present study revealed distinct regions where the induced events lie and that the positions of these regions are found at increasing distances from the optic nerve the later the time of exposure. This position effect directly reflects the previously observed developmental pattern of the RPE, namely that cells in the regions most distal from the optic nerve are proliferating most vigorously. The numbers and positions of RPE cells displaying the transformed (pigmented) phenotype strongly advocate the proposal that dividing cells are at highest risk to deletions induced by carcinogens.