Rees Gwen S, Trikic Michael Z, Winther Jeanette F, Tawn E Janet, Stovall Marilyn, Olsen Jørgen H, Rechnitzer Catherine, Schrøder Henrik, Guldberg Per, Boice John D
Genetics Department, Westlakes Research Institute, Cumbria, UK.
Int J Radiat Biol. 2006 Mar;82(3):153-60. doi: 10.1080/09553000600640538.
To investigate germline mutation rate at eight minisatellite loci in 24 Danish families, where one parent is the survivor of childhood or adolescent cancer treated with radiotherapy.
Parents and offspring were profiled for eight hypervariable minisatellite loci (B6.7, CEB1, CEB15, CEB25, CEB36, MS1, MS31, MS32) by Southern blotting.
Seven paternal mutations were observed for 130 informative alleles in 18 offspring from 11 radiation-exposed fathers (mean preconceptional dose for offspring 0.29 Gy, range<0.01-1.2 Gy), compared to six mutations for 146 informative alleles in 21 offspring from 13 unexposed fathers. No statistically significant difference between the total paternal mutation rates was observed (5.4% for exposed fathers and 4.1% for unexposed fathers). Three maternal mutations were observed for 148 informative alleles in 21 offspring from 13 radiation-exposed mothers (mean preconceptional dose for offspring 0.71 Gy, range <0.01-9.2 Gy), compared to one mutation for 130 informative alleles in 18 offspring from 11 unexposed mothers. Again, no statistically significant difference was observed between the total maternal mutation rates (2.0% for exposed mothers and 0.8% for unexposed mothers).
The data from this pilot study demonstrate no statistically significant increase in germline minisatellite mutation rate associated with radiotherapy for childhood and adolescent cancer.
调查24个丹麦家庭中8个微卫星位点的种系突变率,这些家庭中有一位家长是接受过放射治疗的儿童期或青少年期癌症幸存者。
通过Southern印迹法对父母及其后代的8个高变微卫星位点(B6.7、CEB1、CEB15、CEB25、CEB36、MS1、MS31、MS32)进行分析。
在11位接受过放疗的父亲的18名后代中,130个信息性等位基因中有7个父系突变(后代的孕前平均剂量为0.29 Gy,范围<0.01 - 1.2 Gy),而在13位未接受放疗的父亲的21名后代中,146个信息性等位基因中有6个突变。未观察到总父系突变率之间有统计学显著差异(接受放疗的父亲为5.4%,未接受放疗的父亲为4.1%)。在13位接受过放疗的母亲的21名后代中,148个信息性等位基因中有3个母系突变(后代的孕前平均剂量为0.71 Gy,范围<0.01 - 9.2 Gy),而在11位未接受放疗的母亲的18名后代中,130个信息性等位基因中有1个突变。同样,未观察到总母系突变率之间有统计学显著差异(接受放疗的母亲为2.0%,未接受放疗的母亲为0.8%)。
这项初步研究的数据表明,与儿童期和青少年期癌症放疗相关的种系微卫星突变率没有统计学显著增加。