Transplacental mutagenicity of N-ethyl-N-nitrosourea at the hprt locus in T-lymphocytes of exposed B6C3F1 mice.
Transplacental mutagenicity of N-ethyl-N-nitrosourea at the hprt locus in T-lymphocytes of exposed B6C3F1 mice.
复制标题
N-乙基-N-亚硝基脲在暴露的 B6C3F1 小鼠 T 淋巴细胞中 hprt 位点的经胎盘致突变性。
DOI：
10.1002/em.1047
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发表时间：
2001
影响因子：
2.8
通讯作者：
Walker,VE
中科院分区：
文献类型：
--
作者：
Sussman,HE;Bauer,MJ;Shi,X;Judice,SA;Albertini,RJ;Walker,VE
先前的研究比较了不同年龄（断奶前、断奶或年轻成年）小鼠单次腹腔内（i. p.）注射乙基亚硝基脲（ENU）。本研究的目的是确定给药后经过的时间对经胎盘接受ENU单次急性给药与多次分次给药的小鼠中hprt突变型T细胞（Mf）频率的影响。为此，妊娠C57 BL/6小鼠（n = 13-16/组）（已与C3 H雄性交配）在妊娠第18天单次腹腔注射40 mg ENU/kg bw，在妊娠第12 - 18天分次腹腔注射6 mg ENU/kg bw，或单独注射DMSO溶剂。在产后第10、13、15（仅单次给药）、17、20、40和70天对各组幼仔进行尸检，以使用T细胞克隆试验进行T细胞分离和hprtMf测量。从经胎盘给药动物的胸腺分离的T细胞达到最大Mfs所需的时间为2周，与之前在成年、断奶和断奶前小鼠ENU给药后观察到的时间跨度相同。从对照动物脾脏中分离的T细胞的Mfs平均为2.1 ± 0.3（SE）× 10−6。在经胎盘给予ENU单次给药的小鼠脾脏中，Mfs在产后15天达到最大值[84.7 ± 15.8（SE）× 10−6]，并在产后40天降至较低但仍升高的水平。在分次经胎盘给予ENU的小鼠脾脏中，Mfs在产后13天达到最大值[74.0 ± 16.3（SE）× 10−6]，并在产后40天降至背景水平。描述ENU处理小鼠与对照小鼠hprtMfs随时间变化的曲线下面积估计经胎盘单次和分次给药暴露的致突变效力分别为1.9和0.8 × 103。将子宫内暴露于ENU的小鼠的致突变效力估计值与给予相似剂量的相同批号ENU的4周龄小鼠的致突变效力估计值进行比较，表明小鼠在胎儿期更容易发生ENU诱导的致突变。Environ.摩尔变异体38：30-37，2001 © 2001 Wiley利斯公司
Previous studies have compared age‐related differences in total mutagenic burden in mice of differing age (preweanling, weanling, or young adult) after single intraperitoneal (i.p.) injections of ethylnitrosourea (ENU). The purpose of the present investigation was to determine the effects of time elapsed since treatment on the frequency ofhprtmutant T‐cells (Mf) from mice treated transplacentally with single acute vs. multiple split doses of ENU. To this end, pregnant C57BL/6 mice (n = 13–16/group), which had been bred to C3H males, were given i.p. injections of 40 mg ENU/kg bw in a single dose on day 18 of gestation, in a split dose of 6 mg ENU/kg bw on days 12 through 18 of gestation, or DMSO vehicle alone. Groups of pups were necropsied on days 10, 13, 15 (single dose only), 17, 20, 40, and 70 postpartum for T‐cell isolations andhprtMfmeasurements using the T‐cell cloning assay. The time required to reach maximum Mfs in T‐cells isolated from thymus of transplacentally treated animals was 2 weeks, the same time span as previously observed after ENU treatment of adult, weanling, and preweanling mice. Mfs in T‐cells isolated from spleens of control animals averaged 2.1 ± 0.3 (SE) × 10−6. In spleens of mice treated transplacentally with ENU in a single dose, Mfs reached a maximum at 15 days postpartum [84.7 ± 15.8 (SE) × 10−6] and decreased to lower but still elevated levels at 40 days postpartum. In spleens of mice treated transplacentally with ENU in a split dose, Mfs reached a maximum at 13 days postpartum [74.0 ± 16.3 (SE) × 10−6] and decreased to background levels at 40 days postpartum. The areas under the curves describing the change inhprtMfs over time for ENU‐treated vs. control mice estimate the mutagenic potency for transplacental single‐ and split‐dose exposures to be 1.9 and 0.8 × 103, respectively. Comparison of the mutagenic potency estimates for mice exposed to ENU in utero to 4‐week‐old mice given a similar dose of the same lot number of ENU indicates that the mouse is more susceptible to ENU‐induced mutagenesis during fetal life. Environ. Mol. Mutagen. 38:30–37, 2001 © 2001 Wiley‐Liss, Inc.