Description: Air pollution has been clearly linked to respiratory and cardiovasculaDescription: Recent experiments suggest a novel mechanism whereby epigenetic programming of the mammalian germ line can confer susceptibility to reduced fertility, reproductive tract anomalies and cancer across generations through the male line. We now postulate a similar pathophysiologic mechanism for testicular germ cell tumors (TGCTs) in humans. This hypothesis is compatible with all major epidemiologic findings for TGCT, including rapidly increasing incidence, familial aggregation, and association of TGCT with personal histories of reduced fertility and both congenitally undescended testes and of extremes of birth weight -- conditions previously shown to involve either in utero hormone exposures or epigenetic disruptions or in model systems. In ongoing research, we have identified hundreds of families with multiple occurrence of TGCT and related conditions and undertaken their enrollment in a traditional population-based genetic epidemiologic research based on variation of DNA nucleotide sequence. We now propose preliminary research designed to develop new procedures and measures needed to address epigenetic mechanisms in the etiology of TGCT in this or a more appropriate study population, as well as in future studies of the etiology of urogenital congenital disorders and low birth weight.

Award Amount: $25,000

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Effects of Exposure to Naphthalene and its Metabolites on Thiol Enzymes in Lung Epithelial Cells

Description: Naphthalene (NAP), a major constituent of the Southern California air, is found in ambient Los Angeles Basin air at levels between 10 to 100 times higher than any other PAH. NAP is photochemically oxidized to the naphthoquinones (NQs) which have been found in ambient particulate matter (PM). The NQs, which are also cellular metabolites of NAP, are likely to be major contributors to the toxicity of NAP. In this context, a recent report by the Children's Health Study group demonstrated a correlation between the biotransformation enzyme epoxide hydrolase and incidence of asthma in children which suggests that the pathway NAP to NQ may be the basis for NAP and NQ pulmonary toxicity. NAP metabolite 1,2-Naphthoquinone (1,2-NQ) has been shown to activate the epidermal growth factor receptor (EGFR) by its irreversible inactivation of protein tyrosine phosphatase 1B (PTP1B). The EGFR is directly involved in the goblet cell hyperplasia associated with asthma so the formation of 1,2-NQ, which is dependent on epoxide hydrolase, could be an important contributor to asthma development and exacerbation.

We have developed a HPLC method for the analysis of quinones such as 9,10-phenanthrenedione (9,10-PQ) and have observed that a rapid metabolic loss occurs, with a half-life of 1 hour. This rapid metabolic loss suggests that NAP will also undergo metabolism rapidly and be converted into the NQs and exert NQ based toxicity. In this project we will evaluate: i) The metabolism of NAP and 1,2-NQ by epithelial cells, and ii) the effects of NAP and 1,2-NQ on cellular PTP1B and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), two key enzymes in epidermal growth factor-mediated cell responses and glycolytic pathway. Results from this project will be used to further apply for R21 or R01 grants.

Award Amount: $25,000

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Description: Epidemiological studies have begun to associate proximity to vehicular traffic with adverse chronic respiratory effects, but the mechanism(s) for this association has yet to be elucidated. At the same time, toxicological studies have shown that urban PM causes inflammation and oxidative stress in human experimental and animal studies and in in vitro assays. A study is proposed to investigate whether such biological activity as measured in in vitro assays shows gradients for PM collected at varying distances downwind of busy freeways. Cascade impactors will collect coarse, fine, and quasi-ultrafine particulate matter (PM 0.25 ) over two, two-week intervals. Biological activity will be measured using human bronchial epithelial cells, and compared on a per-unit mass basis and an air concentration basis. We believe this will be the first such test of local biological gradients related to roadways. Any observed gradients may have important implications for previous and ongoing epidemiological studies where two-week samplers have been used to estimate exposures to air pollution. One benefit may be refined exposure metrics that more closely link chronic respiratory health endpoints with exposures due to traffic.

 

Award Amount: $24,996

Description: The apparent immunomodulatory effect of ultraviolet radiation (UVR) purported the hypothesis that UVR could be involved in the development of immune related diseases, i.e. type 1 diabetes, multiple sclerosis (MS), asthma, atopic dermatitis and others. This notion is further strengthened by the observed inverse relationships between UVR and type 1 diabetes and MS and the direct association between UVR and asthma in ecological studies. Case-control studies have verified the protective effect of sun exposure /UVR in MS. However the association between UVR and asthma has yet to be fully investigated . The Children's Health Study provides the scope to address this novel hypothesis of asthma and atopy pathogenesis.

This proposal will support grant applications by providing preliminary data concerning the UVR mediated immune pathways that likely involve vitamin D signaling asthma and atopy.

Award Amount: $ 16,349.11

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Description: Due to the rapid development of nanotechnology, the worldwide release of manufactured nanoparticles into our environment has begun. Nanotechnology is not “on the way”: It is here. Nanotubes, one of the nanoparticles being most aggressively developed, are fibrous materials of extreme aspect ratio, several nanometers in diameter and hundreds to thousands of nanometers long. They are one of the most lucrative of all engineered nanoparticles, in large part due to their high specific surface area, surface reactivity, and tensile strength. Nanotubes are likely to be used in many manufacturing processes and consumer goods, including many automotive applications. Nanotubes are known to escape confinement in nanotube-generating facilities during transfer operations. They are already being found among particulates collected during air pollution studies performed next to freeways, and several animal studies have shown that inhalation of nanotubes has adverse health effects. Nanotubes and some other engineered nanoparticles have unusual properties that can confound detection by typical instruments that are effective at monitoring airborne nanoparticles. The main objectives of this projects are: i) to generate a reliable lab test aerosol of nanotubes with which to challenge existing and state-of-the-art air monitoring instruments; ii) to characterize the response of a variety of air-monitoring instruments and techniques to the lab-generated nanotube aerosol with respect to an array of performance factors including number and size detection limits, response time, dynamic range, and intra-instrument agreement; and iii) to add particulate matter emitted by vehicular exhaust to the lab-generated nanotube aerosol and characterize again the response of these same air-monitoring instruments The results will be used to help develop a full-scale exposure study that can serve as a basis for an application for a NIOSH or NSF RO-1 grant.

Award Amount: $25,000

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