The objectives of this proposal are (1) to develop methods for quantitating daily exposure to nicotine, tar and carbon monoxide while smoking cigarettes or consuming smokeless tobacco; (2) to apply these methods to study exposure to toxic substances while smoking different numbers or different brands of cigarettes, and (3) to study other factors which are known to influence the intake and effects of tar and nicotine. Assays for quantitating urinary and, if possible, blood concentrations of polycyclic aromatic hydrocarbons, solanesol (a tobacco-specific terpene alcohol), tobacco-specific nitroso compounds and various combustion gases will be developed. Consumption of nicotine will be measured using pharmacokinetic data obtained after intravenous infusion of nicotine in combination with nicotine blood concentration data obtained over 24 hours while smoking in volunteer subjects on a clinical study center, or using casual blood level of nicotine and cotinine in outpatient studies. Using these methods, the effects of smoking different numbers of cigarettes, different tobacco products, i.e., pipes, cigars, snuff and chewing tobacco, and smoking cigarettes with different yields will be studied. In addition, the influence of alcohol and caffeine on nicotine and tar intake, as well as on the metabolism of nicotine and the cardiovascular effects of cigarette smoking, will be studied. Assays developed in our studies will be useful in assessing exposure to toxic components of tobacco smoke in epidemiologic studies and will provide specific information about potential health hazards of different tobacco products. The alcohol and caffeine studies will further our understanding of the influence of these commonly used drugs on smoking behavior and its consequences. Our studies may lead to more effective interventions to reduce the extent and harmful consequences of cigarette smoking.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032389-06
Application #
3170343
Study Section
Toxicology Study Section (TOX)
Project Start
1982-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Hospitals
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Benowitz, Neal L; Herrera, Brenda; Jacob 3rd, Peyton (2004) Mentholated cigarette smoking inhibits nicotine metabolism. J Pharmacol Exp Ther 310:1208-15
Benowitz, Neal L; Perez-Stable, Eliseo J; Herrera, Brenda et al. (2002) Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans. J Natl Cancer Inst 94:108-15
Perez-Stable, E J; Herrera, B; Jacob 3rd, P et al. (1998) Nicotine metabolism and intake in black and white smokers. JAMA 280:152-6
Perez-Stable, E J; Benowitz, N L; Marin, G (1995) Is serum cotinine a better measure of cigarette smoking than self-report? Prev Med 24:171-9
Perez-Stable, E J; Marin, G; Marin, B V et al. (1992) Misclassification of smoking status by self-reported cigarette consumption. Am Rev Respir Dis 145:53-7
Duan, M J; Yu, L; Savanapridi, C et al. (1991) Disposition kinetics and metabolism of nicotine-1'-N-oxide in rabbits. Drug Metab Dispos 19:667-72
Jacob 3rd, P; Yu, L; Wilson, M et al. (1991) Selected ion monitoring method for determination of nicotine, cotinine and deuterium-labeled analogs: absence of an isotope effect in the clearance of (S)-nicotine-3',3'-d2 in humans. Biol Mass Spectrom 20:247-52
Jones, C J; Schiffman, M H; Kurman, R et al. (1991) Elevated nicotine levels in cervical lavages from passive smokers. Am J Public Health 81:378-9
Le Houezec, J; Benowitz, N L (1991) Basic and clinical psychopharmacology of nicotine. Clin Chest Med 12:681-99
Zhang, Y; Jacob 3rd, P; Benowitz, N L (1990) Determination of nornicotine in smokers' urine by gas chromatography following reductive alkylation to N'-propylnornicotine. J Chromatogr 525:349-57

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