LIFESTYLE FACTORS AFFECTING FETAL SOMATIC MUTATION

描述：（改编自研究者摘要）体细胞突变 在胚胎/胎儿生命期间具有预期的健康影响。 早期 癌基因、肿瘤抑制基因或基因中的癌症易感突变 参与DNA修复可能会导致大量的启动突变 由于生长和发育过程中的克隆扩增， 胎儿 突变细胞在发育过程中的克隆扩增也可能导致 在表现为出生缺陷的基因的嵌合体表达中。 突变 在发育早期发生的，也可以在分化的胚 细胞导致性腺镶嵌和新孟德尔的出现 紊乱 这项研究的300对产妇/新生儿的目的是评估的影响， 母体环境对胚胎/胎儿体细胞突变的影响 基因座（HPRT和GPA）在胎盘血细胞。 这项拟议中的调查 研究人员对新生儿的体细胞突变进行了初步调查， 他们发现母亲接触烟草烟雾和降低 社会经济地位，也许是因为它与母亲的联系， 生活方式因素，似乎增加了频率，改变了频谱 子宫内体细胞突变的分子机制 受试者将 从种族和社会经济多样化的人口中招募， 妇女在第一次产前检查时，通常在怀孕10-14周时。 他们将接受采访，并进行全面的问卷调查， 描述他们暴露于烟草烟雾的特征，并确定其他人口统计学特征， 变量 将在初次面谈时采集母体血液样本， 妊娠28-32周，以及分娩时。 这些人的血样 母亲，连同新生儿的胎盘血液样本， 测定4-氨基联苯血红蛋白（4-ABP-Hb）加合物，以定量 烟草烟雾诱变剂对母亲的生物有效剂量， 整个妊娠期的胎儿。 HPRT和GPA突变频率测量， 将检测胎盘血样与4-ABP-Hb加合物的相关性 水平和其他生活方式/暴露变量。 的分子光谱 将分析新生儿中的HPRT突变， 环境暴露。 最后，GPA突变频率在 将对母亲/新生儿对进行检测，以确定是否存在提示共享 基因/环境因素 研究人员表示，这项重点研究 将寻求在一个独立的人群中证实他们的初步发现， 并具体查明以前的 观察到的相关性反映了特异性和 可识别的母体暴露。

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.