Fecal mutagen fecapentaene-12 damages mammalian colon epithelial DNA.
Fecal mutagen fecapentaene-12 damages mammalian colon epithelial DNA.
复制标题
粪便诱变剂 fecapentaene-12 会损害哺乳动物结肠上皮 DNA。
DOI：
10.1093/carcin/8.10.1475
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发表时间：
1987
期刊：
影响因子：
4.7
通讯作者：
A. Shamsuddin
中科院分区：
文献类型：
--
作者：
M. J. Hinzman;C. Novotny;A. Ullah;A. Shamsuddin
非卡喷肠烯是一种在人类结肠中自然产生的粪便诱变剂，在艾姆斯试验系统中已被证明具有高度诱变性。然而，迄今为止还没有关于非喷他烯在靶上皮中的作用的研究报道。在我们实验室使用Fischer 344大鼠对fecapentaene-12 （FP-12）进行的体内研究表明，浓度为10(-6)M的FP-12能够诱导[3H]-胸腺嘧啶并入DNA的数量增加2.7倍（P < 0.001）。放射自显像研究显示，结肠上皮细胞的标记指数增加了类似的2.6倍，但有丝分裂率减少了8.8倍。DNA单链断裂测量结果显示，在体内用浓度为1微米的FP-12处理后，碱不稳定位点的数量比对照组增加了16倍（P < 0.001）。类似的体外测定研究表明，在1 nM至1微米的浓度范围内，碱不稳定位点的数量呈线性趋势。这些发现表明，粪便诱变原FP-12诱导核酸原位损伤，从而可能在结肠肿瘤转化中发挥作用。
Fecapentaenes are fecal mutagens that are naturally produced in the human colon and have been shown to be highly mutagenic in the Ames assay system. However to date no studies have been reported regarding the effects of fecapentaene in the target epithelium. In vivo studies with fecapentaene-12 (FP-12) using Fischer 344 rats in our laboratory indicate that a concentration of 10(-6) M FP-12 is capable of inducing a 2.7-fold increase (P less than 0.001) in [3H]-thymidine incorporation into DNA. Autoradiographic studies demonstrate a similar (2.6-fold) increase in the labelling index but an 8.8-fold reduction in the mitotic rate in colonic epithelial cells. Results of DNA single-strand breakage measurements show that in vivo treatment with FP-12 at concentrations of 1 microM introduces a 16-fold increase (P less than 0.001) in the number of alkali-labile sites over controls. Similar studies in in vitro assays indicate a linear trend in the number of alkali-labile sites over a range of concentrations varying from 1 nM to 1 microM. These findings indicate that the fecal mutagen FP-12 induces damage in situ to nucleic acids and thus may play a role in neoplastic transformation of the colon.