Nakano M, Kodama Y, Ohtaki K, Nakashima E, Niwa O, Toyoshima M, Nakamura N
Department of Genetics, Radiation Effects Research Foundation, Hiroshima, Japan.
Radiat Res. 2007 Jun;167(6):693-702. doi: 10.1667/RR0718.1.
Mice were exposed at various ages to 1 Gy or 2 Gy of X rays, and translocation frequencies in peripheral blood T cells, spleen cells, and bone marrow cells were determined with FISH painting of chromosomes 1 and 3 when the animals were 20 weeks old. It was found that the mean translocation frequencies were very low (< or =0.8%) in mice exposed in the fetal or early postnatal stages. However, with the increase in animal age at the time of irradiation, the frequency observed at 20 weeks old became progressively higher then reached a plateau (about 5%) when mice were irradiated when > or =6 weeks old. A major role of p53 (Trp53)-dependent apoptosis for elimination of aberrant cells was not suggested because irradiated fetuses, regardless of the p53 gene status, showed low translocation frequencies (1.8% in p53(-/-) mice and 1.4% in p53(+/-) mice) compared to the frequency in the p53(-/-) mother (7.4%). In contrast, various types of aberrations were seen in spleen and liver cells when neonates were examined shortly after irradiation, similar to what was observed in bone marrow cells after irradiation in adults. We interpreted the results as indicating that fetal cells are generally sensitive to induction of chromosome aberrations but that the aberrant cells do not persist because fetal stem cells tend to be free of aberrations and their progeny replace the pre-existing cell populations during the postnatal growth of the animals.
将不同年龄段的小鼠暴露于1 Gy或2 Gy的X射线下,当动物20周龄时,通过对1号和3号染色体进行荧光原位杂交(FISH)染色来测定外周血T细胞、脾细胞和骨髓细胞中的易位频率。结果发现,在胎儿期或出生后早期暴露的小鼠中,平均易位频率非常低(≤0.8%)。然而,随着照射时动物年龄的增加,20周龄时观察到的频率逐渐升高,当小鼠≥6周龄时接受照射,该频率随后达到一个平台期(约5%)。未发现p53(Trp53)依赖性凋亡在消除异常细胞方面起主要作用,因为与p53(-/-)母亲中的频率(7.4%)相比,无论p53基因状态如何,受照射的胎儿均显示出较低的易位频率(p53(-/-)小鼠中为1.8%,p53(+/-)小鼠中为1.4%)。相反,在照射后不久检查新生小鼠时,在脾细胞和肝细胞中观察到了各种类型的畸变,这与在成年动物照射后骨髓细胞中观察到的情况相似。我们将这些结果解释为表明胎儿细胞通常对染色体畸变的诱导敏感,但异常细胞不会持续存在,因为胎儿干细胞往往没有畸变,并且它们的后代在动物出生后的生长过程中取代了先前存在的细胞群体。