Environmental exposure of the mouse germ line: DNA adducts in spermatozoa and formation of de novo mutations during spermatogenesis.
Environmental exposure of the mouse germ line: DNA adducts in spermatozoa and formation of de novo mutations during spermatogenesis.
复制标题
DOI：
10.1371/journal.pone.0011349
复制
发表时间：
2010-06-28
期刊：
影响因子：
3.7
通讯作者：
Brunborg G
中科院分区：
文献类型：
--
作者：
Olsen AK;Andreassen A;Singh R;Wiger R;Duale N;Farmer PB;Brunborg G
精子DNA损伤与精子质量差、胚胎发育紊乱和早期胚胎丢失有关，一些遗传疾病源于父亲的新生突变。我们以前报道过啮齿动物睾丸细胞中大体积dna损伤的修复不良。我们研究了男性生殖系DNA损伤的命运。采用液相色谱-串联质谱法测定B[a]PDE-N2-dG加合物，并在暴露于苯并[a]芘（B[a]P; 3×50 mg/kg bw, i.p.）的Big Blue®小鼠中测定cii -转基因的新生突变。在暴露后的不同时间点收集精子，以研究在精子发生的不同阶段暴露的后果。B[a]暴露于精母细胞或精子发生后期诱导的PDE-N2-dG加合物在产生的精子中持续保持高水平。来自暴露的精原细胞的精子不含DNA加合物；然而，已经诱导了新生突变（p = 0.029），特别是GC-TA翻转，这是B[a] p诱变的特征。此外，在精子中一致观察到一种特定的自发突变谱。发现了接触后基因毒性后果的时间模式，精子中DNA加合物水平最初增加，据信影响生育能力，随后诱导种系新生突变，可能对后代造成后果。
Spermatozoal DNA damage is associated with poor sperm quality, disturbed embryonic development and early embryonic loss, and some genetic diseases originate from paternal de novo mutations. We previously reported poor repair of bulky DNA-lesions in rodent testicular cells. We studied the fate of DNA lesions in the male germ line. B[a]PDE-N2-dG adducts were determined by liquid chromatography-tandem mass spectrometry, and de novo mutations were measured in the cII-transgene, in Big Blue®mice exposed to benzo[a]pyrene (B[a]P; 3×50 mg/kg bw, i.p.). Spermatozoa were harvested at various time-points following exposure, to study the consequences of exposure during the different stages of spermatogenesis. B[a]PDE-N2-dG adducts induced by exposure of spermatocytes or later stages of spermatogenesis persisted at high levels in the resulting spermatozoa. Spermatozoa originating from exposed spermatogonia did not contain DNA adducts; however de novo mutations had been induced (p = 0.029), specifically GC-TA transversions, characteristic of B[a]P mutagenesis. Moreover, a specific spectrum of spontaneous mutations was consistently observed in spermatozoa. A temporal pattern of genotoxic consequences following exposure was identified, with an initial increase in DNA adduct levels in spermatozoa, believed to influence fertility, followed by induction of germ line de novo mutations with possible consequences for the offspring.
登录
查看更多内容
影响因子：
5
作者：
Cordier, S;Monfort, C;Arslan, A
通讯作者：
Arslan, A
影响因子：
6.7
作者：
Hull, MGR;North, K;Ford, WCL
通讯作者：
Ford, WCL
影响因子：
6.7
作者：
Frydman, Nelly;Prisant, Nadia;Fanchin, Renato
通讯作者：
Fanchin, Renato
影响因子：
105.7
作者：
HULL, MGR;GLAZENER, CMA;DESAI, KM
通讯作者：
DESAI, KM
影响因子：
14.9
作者：
Jansen, J;Olsen, AK;Mullenders, L
通讯作者：
Mullenders, L