Naphthalene exposure, chromosomal aberrations in poor urban school children.

萘暴露，贫困城市学童的染色体畸变。

• 批准号: 8104933
• 负责人: Manuela A Orjuela
• 金额: $ 20.9万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8104933
• 关键词: 5 year old; 9 year old; Accident and Emergency department; Adult; Affect; African American; African Caribbean; Age; Air; Air Pollutants; Aromatic Polycyclic Hydrocarbons; Biological Markers; Birth; Blood; Carcinogens; Caribbean region; Cell Count; Cell division; Cells; Child; Childhood; Chromosomal Rearrangement; Chromosome abnormality; Chromosomes; Chromosomes, Human, Pair 1; Chronic; Collection; Colony-forming units; Communities; Cytogenetics; DNA; DNA Damage; DNA Sequence Rearrangement; Data; Detection; Dominican; Environmental Health; Excretory function; Exposure to; Family; Fluorescent in Situ Hybridization; Frequencies; Future; Gasoline; Genetic; Genome; Growth; Half-Life; Health; Hemolytic Anemia; Home environment; Hour; Household; Household Products; Human; Immigrant; In Vitro; Individual; Infant; International Agency for Research on Cancer; Latino; Lymphocyte; Maternal Exposure; Measures; Mexican Americans; Moths; Myeloid Progenitor Cells; Naphthalene; Naphthols; New York City; Occupational; Occupational Exposure; Paint; Participant; Peripheral; Peripheral Blood Lymphocyte; Pesticides; Puberty; Radiation; Reporting; Risk; Sampling; School-Age Population; Schools; Smoking; Source; Spottings; Surveys; Testing; Time; Umbilical Cord Blood; Urine; Validation; Variant; air monitoring; boys; cancer risk; carcinogenicity; cigarette smoking; clastogen; cohort; exhaust; girls; granulocyte; inner city; member; nutrition; prenatal; response; sperm cell; trafficking; urinary; vapor

DESCRIPTION (provided by applicant): Inner-city children are exposed to naphthalene, an understudied volatile Polycyclic Aromatic Hydrocarbon (PAH) and an IARC classified potential carcinogen, in indoor air from naphthalene containing household products such as mothballs, and from penetrating traffic emissions. Indoor air levels of naphthalene have been reported to be 5-10 fold those in outdoor air [1]. Home use of naphthalene products varies culturally. In a NYC pediatric emergency room, 27% of African American and Caribbean families reported using moth- balls as air fresheners[2], while some Latin immigrants use them in traditional remedies[3,4]. Naphthalene expo- sure is associated with hemolytic anemia in infants [2] and with DNA damage in sperm, while in vitro exposure to naphthalene metabolites is toxic to colony forming units of human granulocyte precursors[5,6]. In the Columbia Center for Children's Environmental Health (CCCEH) birth cohort of Latino and African-American children in NYC, prenatal maternal exposure to airborne PAH is associated with infant chromosomal aberrations (CAs) measured in cord blood using Whole Chromosome Paints Fluorescent In Situ Hybridization (WCPFISH). CAs are an established marker of cancer risk and are a bio-dosimeter of clastogenic exposures in adults. Translocations, the most persistent subtype of CAs with half lives of 2-4 years [7,8], are considered the most meaningful cytogenetic endpoint for assessing cancer risk[9]. Our preliminary data suggest that increasing levels of the naphthalene metabolites, 1- and 2-naphthol, measured in spot urine samples of 5 year olds in the CCCEH cohort, are associated with increased occurrence and frequency of CAs and translocations in peripheral blood lymphocytes drawn concurrently. Urinary naphthol levels in CCCEH 5 year olds are elevated compared to median levels in US children, though comparable to levels in Mexican Americans[10,11]. Urine levels of naphthol are a reliable measure of individual exposure but they have short half-lives and consequently vary significantly throughout the day. First-morning urine collections provide a more accurate measure of household exposure to naphthalene and collection at a uniform time maximizes detection of inter-subject differences. Age 9, the median US age for initiating puberty[12,13], is potentially significant for future cancer risk because it is an age of accelerated growth with increased cell division and opportunity for propagation of genetic damage. Our preliminary data suggests that naphthalene is a clastogen. In order to validate our initial data and to determine if naphthalene exposure predicts CAs and translocations in children, we propose to 1) measure 1- and 2- naphthol in first- morning urine samples, 2) score CAs and translocations using WCP FISH and 3) document home use of naphthalene-products in 158 nine year olds of the CCCEH, a cohort with documented exposure to varying and often high levels of ambient and indoor air PAH. We propose to measure the relationship between biomarkers of naphthalene exposure in childhood and CAs and translocations in order to document human response to a potentially myelotoxic and genotoxic exposure differentially affecting impoverished communities. PUBLIC HEALTH RELEVANCE: Chromosomal aberrations a marker of cancer risk are associated with exposure to naphthalene (a potential carcinogen) in 5 yr olds in our CCCEH cohort of poor Latino and African American children in NY. We propose to validate this preliminary finding by studying 158 nine yr olds in the CCCEH cohort by 1) measuring a marker of individual exposure to household sources of naphthalene, 2) documenting these sources, including ones more common in poor immigrant communities and 3) measuring their association with early genetic damage. This study aims to increase understanding of childhood exposure to an understudied indoor air pollutant.

描述（由申请人提供）：市中心的儿童暴露于萘，一种研究的挥发性多环芳烃（PAH）和IARC分类的潜在致癌物中的室内空气中，来自含有萘的家用产品（例如莫蒂（Moth））的室内空气，以及通过渗透交通流量。据报道，萘萘的室内空气水平为5-10倍的室内空气中的空气水平[1]。萘产品的家庭用途在文化上有所不同。在纽约市的儿科急诊室中，有27％的非裔美国人和加勒比家庭报告说，用蛾球作为空气新鲜剂[2]，而一些拉丁移民则在传统的补救措施中使用它们[3,4]。萘的解释与婴儿的溶血性贫血有关[2]和精子中的DNA损伤，而在体外暴露于萘代谢物中对形成人类粒细胞前体的单位的菌落有毒[5,6]。在哥伦比亚儿童环境健康中心（CCCEH）在纽约的拉丁裔和非裔美国人儿童的出生队列中，产前孕产妇暴露于空气中PAH与婴儿染色体差异（CAS）相关，该染色体畸变（CAS）使用全染色体涂料中的脐带血染色体涂料（CAS）相关。 CAS是癌症风险的确定标志，是成年人层造型暴露的生物固定仪。易位是CAS的最持续性亚型，一半的生命为2 - 4年[7,8]，被认为是评估癌症风险的最有意义的细胞遗传学终点[9]。我们的初步数据表明，在CCCEH队列中以5岁儿童的尿液样本测量的萘代谢物的水平增加与外周血血液淋巴细胞的CAS和CAS的发生频率和转换相关。与美国儿童的中位水平相比，CCCEH 5岁的CCCEH 5岁儿童的尿萘酚水平升高，尽管与墨西哥裔美国人的水平相当[10,11]。萘酚的尿液水平是个人暴露的可靠度量，但半衰期短，因此全天有很大差异。首次早晨的尿液收集提供了更准确的量度，以统一的时间对萘和收集的家庭接触，可最大程度地检测受试者间差异。 9岁，美国开始青春期的中位年龄[12,13]，对于未来的癌症风险而言可能是重要的，因为它是一个加速生长的时代，并且细胞分裂增加和传播遗传损害的机会。我们的初步数据表明萘是一种锁骨原。为了验证我们的初始数据并确定萘的暴露是否预测儿童的CAS和易位，我们建议1）量度1）在第一个早晨的尿液样本中1-和2- 2-萘酚，2）2）使用WCP FISH的CAS和易位，3）记录了158 NINE年龄段的CCCEH，CCCEH，COHORT，COHORT的含水量的常数，和室内空气PAH。我们建议衡量儿童期和CAS的萘暴露的生物标志物与易位之间的关系，以记录人类对潜在的骨髓毒性和遗传毒性暴露的反应，从而不同地影响了贫困社区。 公共卫生相关性：染色体畸变癌症风险的标志与我们在纽约州可怜的拉丁裔和非洲裔美国儿童的CCCEH队列中5岁的萘（潜在的致癌物）暴露有关。我们建议通过1）测量个人暴露于萘的家庭来源的标记，通过研究CCCEH队列中的158年Olds来验证这一初步发现，2）记录这些来源，包括在贫穷的移民社区中更常见的，以及3）测量其与早期遗传损害的关联。这项研究旨在提高对儿童期暴露于研究不足的室内空气污染物的理解。