Effect of sampling time on somatic and germ cell mutations induced by acrylamide in gpt delta mice.
Effect of sampling time on somatic and germ cell mutations induced by acrylamide in gpt delta mice.
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DOI：
10.1186/s41021-021-00175-5
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发表时间：
2021-02-17
期刊：
影响因子：
--
通讯作者：
Masumura K
中科院分区：
文献类型：
--
作者：
Hagio S;Tsuji N;Furukawa S;Takeuchi K;Hayashi S;Kuroda Y;Honma M;Masumura K
丙烯酰胺（AA）是一种啮齿动物致癌物，被IARC归类为2A组（可能的人类致癌物）。据报道，AA在转基因啮齿动物基因突变试验（TGR试验）中诱导突变，推测其程度取决于暴露时间长度和暴露后的表达持续时间。特别是，它在生殖细胞中并不清楚。为了研究AA在不同采样时间在体细胞和生殖细胞中的致突变性，我们使用gpt delta转基因小鼠进行了TGR试验。8周龄雄性gpt delta小鼠经管饲给予7.5、15和30 mg/kg/天AA，持续28天。在给药最后一天采集外周血样本进行微核试验，并在第31天和第77天采集组织样本进行基因突变试验，这两天分别为末次给药后3天和49天（28 + 3天和28 + 49天）。另一组小鼠腹腔注射50 mg/kg/d的N-乙基-N-亚硝基脲（ENU），连续5天，并在第31天和第77天（5 + 26天和5 + 72天）采集组织样品。在15和30 mg/kg/天AA剂量下，外周血中微核红细胞的频率显著增加。在两个采样时间点，在接受30 mg/kg/天AA给药的睾丸和肺中观察到gpt突变频率（MF）比溶剂对照组增加2 - 3倍。在精子中，gpt MFs和G：C到T：A的颠换在28 + 3d显著增加，而在28 + 49 d没有。在5 + 26天和5 + 72天检测ENU诱导的这些组织中的gpt突变。ENU处理的精子在5 + 72日龄的突变频率高于5 + 26日龄。测定AA给药小鼠睾丸、精子和肺中的gpt MF，并在不同采样时间（28天给药后3天或49天）之间进行比较。这些结果表明，在本实验条件下，精原干细胞对AA致突变性不敏感。暴露于AA后延长表达时间以检测致突变性可能在体细胞中有效，但在生殖细胞中无效。在线版本包含补充材料，可通过10.1186/s41021-021-00175-5获得。
Acrylamide (AA) is a rodent carcinogen and classified by the IARC into Group 2A (probable human carcinogen). AA has been reported to induce mutations in transgenic rodent gene mutation assays (TGR assays), the extent of which is presumed to depend on exposure length and the duration of expression after exposure. In particular, it is not clear in germ cells. To investigate mutagenicity with AA in somatic and germ cells at different sampling times, we conducted TGR assays using gpt delta transgenic mice. The male gpt delta mice at 8 weeks of age were treated with AA at 7.5, 15 and 30 mg/kg/day by gavage for 28 days. Peripheral blood was sampled on the last day of the treatment for micronucleus tests and tissues were sampled for gene mutation assays at day 31 and day 77, those being 3 and 49 days after the final treatment (28 + 3d and 28 + 49d), respectively. Another group of mice was treated with N-Ethyl-N-nitrosourea (ENU) at 50 mg/kg/day by intraperitoneal administration for 5 consecutive days and tissues were sampled at the day 31 and day 77 (5 + 26d and 5 + 72d). Frequencies of micronucleated erythrocytes in the peripheral blood significantly increased at AA doses of 15 and 30 mg/kg/day. Two- to three-fold increases in gpt mutation frequencies (MFs) compared to vehicle control were observed in the testes and lung treated with 30 mg/kg/day of AA at both sampling time. In the sperm, the gpt MFs and G:C to T:A transversions were significantly increased at 28 + 3d, but not at 28 + 49d. ENU induced gpt mutations in these tissues were examined at both 5 + 26d and 5 + 72d. A higher mutant frequency in the ENU-treated sperm was observed at 5 + 72d than that at 5 + 26d. The gpt MFs in the testes, sperm and lung of the AA-treated mice were determined and compared between different sampling times (3 days or 49 days following 28 day-treatment). These results suggest that spermatogonial stem cells are less sensitive to AA mutagenicity under the experimental condition. Prolonged expression time after exposure to AA to detect mutagenicity may be effective in somatic cells but not in germ cells. The online version contains supplementary material available at 10.1186/s41021-021-00175-5.
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影响因子：
3.8
作者：
Fennell, TR;Snyder, RW;Sumner, SCJ
通讯作者：
Sumner, SCJ
DOI：
10.1016/j.mrgentox.2018.05.021
发表时间：
2018-08-01
影响因子：
1.9
作者：
Marchetti, Francesco;Aardema, Marilyn J.;Douglas, George R.
通讯作者：
Douglas, George R.
影响因子：
6.1
作者：
Mucci LA;Wilson KM
通讯作者：
Wilson KM
影响因子：
4.1
作者：
da Costa, GG;Churchwell, MI;Doerge, DR
通讯作者：
Doerge, DR
影响因子：
2.7
作者：
Hobbs, Cheryl A.;Davis, Jeffrey;Recio, Leslie
通讯作者：
Recio, Leslie