LIFESTYLE FACTORS AFFECTING FETAL SOMATIC MUTATION

描述：(改编自《调查者摘要》)体细胞突变 在胚胎/胎儿时期有潜在的健康影响。早些时候 致癌基因、抑癌基因或基因的致癌突变 参与DNA修复可能会导致大量的启动突变 出生时的细胞由于在生长和发育过程中的克隆性扩张 胎儿。突变细胞在发育过程中的克隆性扩增也可能导致 在表现为出生缺陷的基因的嵌合表达中。突变 发生在发育早期也可以固定在分化的细菌 导致性腺嵌合体的细胞和新孟德尔细胞的出现 精神错乱。 这项针对300对产妇/新生儿的研究旨在评估 母体环境对两个独立的胚胎/胎儿体细胞突变的影响 胎盘血细胞基因座(HPRT和GPA)。这项拟议的调查 根据研究人员对#年新生儿体细胞突变的初步调查 他们发现，母亲接触烟草烟雾和更低的 社会经济地位，可能是因为它与母亲 生活方式因素，似乎增加了频率并改变了频谱 子宫内体细胞突变的分子机制。主题将是 从种族和社会经济多元化的人口中招募 妇女在第一次产前检查时，通常在怀孕10-14周时。 他们将接受面谈并填写一份全面的问卷，以 确定他们暴露在烟草烟雾中的特征，并确定其他人口统计数据 变量。母亲的血液样本将在初次面谈时获得，地点为 怀孕28-32周，分娩时。这些血样里的血样 母亲，连同她们新生儿的胎盘血液样本，将被 测定4-氨基联苯血红蛋白(4-ABP-Hb)加合物以定量 烟草烟雾致突变剂的生物有效剂量对母亲和 胎儿在整个妊娠过程中。HPRT和GPA突变频率在 将检测胎盘血样是否与4-ABP-Hb加合物有关 水平，以及其他生活方式/暴露变量。分子光谱分析 将对新生儿的HPRT突变进行分析，以寻找 暴露在环境中。最后，GPA突变频率在 将测试母亲/新生儿配对的关联，以提示共享 基因/环境因素。调查人员表示，这项重点研究 将寻求在独立人群中确认他们的初步发现 母亲和新生儿，并具体确定以前的 观察到的关联反映了特定和 可识别的母体接触。

DESCRIPTION: (Adapted from Investigator's Abstract) Somatic mutations during embryonic/fetal life have prospective health implications. Early cancer-predisposing mutations in oncogenes, tumor suppressor genes, or genes involved in DNA repair may result in significant numbers of initiated mutant cells at birth due to clonal expansion during growth and development of the fetus. Clonal expansion of mutant cells during development can also result in mosaic expression of genes presenting as birth defects. Mutations occurring early in development can also be fixed in differentiating germ cells leading to gonadal mosaicism and the emergence of new Mendelian disorders. This study of 300 maternal/newborn pairs is designed to assess the impact of maternal environments on embryonic/fetal somatic mutation at two independent loci (HPRT and GPA) in placental blood cells. This proposed investigation follows the investigators' initial survey of somatic mutation in newborns in which they found that maternal exposure to tobacco smoke and lower socioeconomic status, perhaps because of its association with maternal lifestyle factors, appears to increase the frequency and alter the spectrum of the molecular mechanisms of somatic mutation in utero. Subjects will be recruited from an ethnically and socioeconomically diverse population of women at their first prenatal visit, typically at 10-14 weeks gestation. They will be interviewed and administered a comprehensive questionnaire to characterize their exposure to tobacco smoke and determine other demographic variables. Maternal blood samples will be obtained at initial interview, at 28-32 weeks of gestation, and at delivery. The blood samples from these mothers, together with placental blood samples from their newborns, will be assayed for 4-amino biphenyl hemoglobin (4-ABP-Hb) adducts to quantitate the biologically effective dose of tobacco smoke mutagens to the mother and fetus throughout gestation. HPRT and GPA mutant frequencies measured in placental blood samples will be tested for association with 4-ABP-Hb adduct levels, and other lifestyle/exposure variables. The molecular spectrum of HPRT mutations in the newborns will be analyzed for evidence of environmental exposures. Finally, GPA mutation frequencies in maternal/newborn pairs will be tested for association suggestive of shared gene/environment factors. The investigators state that this focused study will seek to confirm their preliminary findings in an independent population of mothers and newborns and to specifically ascertain whether the previously observed associations reflect the direct mutagenic effect of specific and identifiable maternal exposures.