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，一种未经充分研究的挥发性多环芳烃（PAH）和国际癌症研究机构分类的潜在致癌物，室内空气中含有萘的家用产品，如樟脑丸，以及渗透的交通排放。据报道，室内空气中萘的含量是室外空气中的5-10倍。家庭使用萘产品因文化而异。在纽约市的儿科急诊室，27%的非裔美国人和加勒比家庭报告使用飞蛾球作为空气清新剂b[2]，而一些拉丁移民将其用于传统疗法[3,4]。萘暴露与婴儿溶血性贫血（bbb）和精子DNA损伤有关，而在体外暴露于萘代谢物对人粒细胞前体集落形成单位是有毒的[5,6]。在纽约市哥伦比亚儿童环境健康中心（CCCEH）拉丁裔和非裔美国儿童的出生队列中，产前母亲暴露于空气中多环芳烃与使用全染色体染色荧光原位杂交（WCPFISH）在脐带血中测量婴儿染色体畸变（CAs）有关。CAs是癌症风险的确定标记物，也是成人致癌物暴露的生物剂量计。易位是ca最持久的亚型，其半衰期为2-4年[7,8]，被认为是评估癌症风险bbb最有意义的细胞遗传学终点。我们的初步数据表明，在CCCEH队列中5岁儿童的尿样中检测到的萘代谢物1-萘酚和2-萘酚水平的增加与同时提取的外周血淋巴细胞中CAs的发生率和频率增加和易位有关。与美国儿童相比，CCCEH 5岁儿童尿萘酚水平升高，但与墨西哥裔美国人的水平相当[10,11]。尿中萘酚的含量是个体接触萘酚的可靠指标，但它们的半衰期很短，因此在一天中变化很大。第一天早晨收集尿液可以更准确地测量家庭对萘的暴露，在统一的时间收集尿液可以最大限度地检测受试者之间的差异。9岁，美国青春期开始的中位数年龄[12,13]，对未来的癌症风险具有潜在的重要意义，因为这是一个加速生长的年龄，细胞分裂增加，遗传损伤传播的机会增加。我们的初步数据表明萘是一种致裂剂。为了验证我们的初始数据，并确定萘暴露是否能预测儿童的多环芳烃和易位，我们建议：1)在晨尿样本中测量1-萘酚和2-萘酚，2)使用WCP FISH对多环芳烃和易位进行评分，3)记录158名CCCEH 9岁儿童的萘产品家庭使用情况，这是一个记录暴露于不同且通常高水平的环境和室内空气多环芳烃的队列。我们建议测量儿童时期萘暴露的生物标志物与CAs和易位之间的关系，以记录人类对可能影响贫困社区的骨髓毒性和遗传毒性暴露的不同反应。