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）：内城儿童会接触萘，这是一种尚未研究的挥发性多环芳烃 (PAH)，也是 IARC 分类的潜在致癌物，室内空气中含有萘的家用产品（如樟脑丸）和渗透性交通排放物。据报道，室内空气中萘的含量是室外空气中的 5-10 倍 [1]。萘产品的家庭使用因文化而异。在纽约市儿科急诊室，27% 的非裔美国人和加勒比家庭报告使用樟脑丸作为空气清新剂[2]，而一些拉丁移民则将其用于传统疗法[3,4]。萘暴露与婴儿溶血性贫血[2]和精子DNA损伤有关，而体外暴露于萘代谢物对人粒细胞前体的集落形成单位有毒[5,6]。在纽约哥伦比亚儿童环境健康中心 (CCCEH) 的拉丁裔和非裔美国儿童出生队列中，使用全染色体涂料荧光原位杂交在脐带血中测量到的婴儿染色体畸变 (CA) 与产前母亲接触空气中的 PAH 相关。 （WCPFISH）。 CA 是癌症风险的既定标志，也是成人断裂基因暴露的生物剂量计。易位是最持久的 CA 亚型，半衰期为 2-4 年 [7,8]，被认为是评估癌症风险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 5 岁儿童的点尿样本中检测到的萘代谢物 1- 和 2-萘酚水平的增加与同时抽取的外周血淋巴细胞中 CA 和易位的发生率和频率增加有关。 。 CCCEH 5 岁儿童的尿萘酚水平高于美国儿童的中位水平，但与墨西哥裔美国人的水平相当[10,11]。尿液中萘酚的含量是衡量个体接触量的可靠指标，但萘酚的半衰期很短，因此在一天中的变化很大。清晨的尿液收集可以更准确地测量家庭萘暴露情况，并且在统一时间收集可以最大限度地检测受试者之间的差异。 9 岁是美国青春期开始年龄的中位数[12,13]，对于未来的癌症风险可能具有重要意义，因为这是一个加速生长的年龄，细胞分裂增加，并且有机会传播遗传损伤。我们的初步数据表明萘是一种断裂剂。为了验证我们的初始数据并确定萘暴露是否可以预测儿童的 CA 和易位，我们建议 1) 测量第一晨尿液样本中的 1- 和 2- 萘酚，2) 使用 WCP FISH 对 CA 和易位进行评分，3 ）记录了 CCCEH 中 158 名 9 岁儿童在家庭中使用萘产品的情况，该群体记录了暴露于不同且通常高浓度的环境和室内空气 PAH 的情况。我们建议测量儿童时期萘暴露的生物标志物与 CA 和易位之间的关系，以便记录人类对潜在的骨髓毒性和基因毒性暴露的反应，这些暴露对贫困社区有不同的影响。 公共卫生相关性：在我们的 CCCEH 纽约贫困拉丁裔和非裔美国儿童队列中，染色体畸变是癌症风险的标志，与 5 岁儿童接触萘（一种潜在致癌物）有关。我们建议通过研究 CCCEH 队列中的 158 名 9 岁儿童来验证这一初步发现，方法是：1) 测量个人接触家庭萘来源的标记，2) 记录这些来源，包括在贫困移民社区中更常见的来源，以及 3) 测量它们与早期遗传损伤的关联。这项研究旨在增进对儿童接触未充分研究的室内空气污染物的了解。