Oral Cell DNA Adducts in Smokers
Ključne riječi
Sažetak
Opis
Using high resolution mass spectrometry, quantify known DNA adducts in oral mucosa cells of 100 smokers from each ethnic group - Native Hawaiians, Whites, and Japanese Americans. DNA adducts of tobacco-specific compounds, formaldehyde, and acrolein will be quantified.
2. Analyze the urine of 100 smokers and 100 non-smokers from each of these groups for mercapturic acids of acrolein and crotonaldehyde, the F2-isoprostane 8-iso-PGF-2α, a biomarker of oxidative damage, and the prostaglandin E2 metabolite PGEM, a biomarker of inflammation, as well as total nicotine equivalents and total NNAL (smokers only). These data will provide critical information relevant to the high risk of Native Hawaiians for lung cancer, and in relationship to the DNA adduct measurements of Specific Aim 1.
3. Use newly developed high resolution mass spectrometric, high throughput DNA adductomic approach to screen for known and unknown DNA adducts to identify a comprehensive DNA modification signature derived from cigarette smoking.
1. Using a targeted DNA adductomic method, screen for multiple DNA modifications simultaneously. The adducts analyzed in Specific Aim 1 will be added to a list including endogenous, 1,3-butadiene-derived (in collaboration with Project 3), aldehyde-derived and nitrosamine or alkylating agent-derived DNA adducts. In parallel, apply DNA adductomic methods in an untargeted mode to investigate the presence of previously unknown DNA adducts. The unknown adducts detected by the untargeted analysis will be included in the list of targeted DNA adducts to ultimately obtain a sensitive method to assess overall DNA damage resulting from cigarette smoking.
2. The list of DNA adducts created in Specific Aim 3a will be applied to investigate differences in the DNA damage signature in selected samples analyzed in Specific Aim 1.
Datumi
| Posljednja provjera: | 10/31/2019 |
| Prvo podneseno: | 08/31/2017 |
| Predviđena prijava poslana: | 09/13/2017 |
| Prvo objavljeno: | 09/17/2017 |
| Posljednje ažuriranje poslano: | 11/03/2019 |
| Posljednje ažuriranje objavljeno: | 11/05/2019 |
| Stvarni datum početka studija: | 05/31/2018 |
| Procijenjeni datum primarnog završetka: | 10/30/2019 |
| Procijenjeni datum završetka studije: | 10/30/2020 |
Stanje ili bolest
Intervencija / liječenje
Other: oral cell DNA adducts
Faza
Grupe ruku
| Ruka | Intervencija / liječenje |
|---|---|
| Native Hawaiian cigarette smokers oral cell DNA adducts | |
| White (European Americans) cigarette smokers oral cell DNA adducts | |
| Japanese American cigarette smokers oral cell DNA adducts |
Kriterij prihvatljivosti
| Dobni uvjeti za studiranje | 18 Years Do 18 Years |
| Spolovi koji ispunjavaju uvjete za studij | All |
| Metoda uzorkovanja | Probability Sample |
| Prihvaća zdrave volontere | Ne |
| Kriteriji | Inclusion Criteria: - currently smoke at least 5 cigarettes per day, self-identified Japanese Americans, European Americans, or Native Hawaiians. Exclusion Criteria: - no current use of other nicotine containing products, no acute or uncontrolled medical or psychiatric conditions, no greater than 14 alcoholic drinks per week, not pregnant, not breastfeeding, not currently taking any medications that affect relevant metabolic enzymes, no active infection. |
Ishod
Primarne mjere ishoda
1. Quantitation of oral cell DNA adducts [Baseline]
Sekundarne mjere ishoda
1. Urinary metabolites [Baseline]
