Determining Levels of [D10] Phenanthrene Tetraol in Smokers' Urine

Study Description

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Brief Summary:

The purpose of this research study is to better understand how people respond to cancer-causing chemicals in cigarette smoke. Some people are able to get rid of these chemicals as harmless agents while others suffer damage to their cells that can ultimately result in cancer. We hope to develop a better understanding of how we can identify the people who are in danger of getting cancer. Participants will complete questionnaires regarding their health and smoking history. We will take blood samples to look at genes which determine how the body breaks down some tobacco-related toxins. Participants will be given a small amount of liquid to drink, containing alcohol, water, and a compound called deuterated phenanthrene (DP), which is found in cigarette smoke and in the environment. Phenanthrene is non-toxic and does not cause cancer, but this compound is broken down by the body in the same way as cancer-causing agents. We will follow the pathway of this compound as it is broken down in the body.

Condition or disease	Intervention/treatment	Phase
Tobacco Toxicant Exposure	Drug: Deuterated phenanthrene	Phase 1

Detailed Description:

Forty apparently healthy smokers and non smokers (20 male, 20 female) will be recruited by advertising in the Twin Cities area. This will be done by the Tobacco Use Research Center. They will be screened in a phone call, then invited to come in for an orientation session at which consent will be obtained. Pregnant smokers will be excluded. They will visit the clinic weekly for 2 months and once monthly for 4 months for a total of 6 months participation.

At each visit they will drink 5 ml of 50:50 ethanol:water containing 10 ug [D10]phenanthrene. They will then collect their 24h urine and return it to the clinic. The urine will be analyzed for [D10]phenanthrene tetraol. The goal of the study is to determine the longitudinal stability of the amount of [D10]phenanthrene-tetraol in urine.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	30 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Determining Levels of [D10] Phenanthrene Tetraol in Smokers' Urine
Study Start Date :	September 2007
Actual Primary Completion Date :	December 2011
Actual Study Completion Date :	December 2011

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: Smoked; Deuterated Phenanthrene spiked in a study cigarette	Drug: Deuterated phenanthrene; Deuterated phenanthrene 10 micrograms
Experimental: Oral; Deuterated phenanthrene in an oral dose	Drug: Deuterated phenanthrene; Deuterated phenanthrene 10 micrograms

Outcome Measures

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Primary Outcome Measures :

1. Pharmacokinetics [ Time Frame: 36 hours post dosing ]
   Deuterated phenanthrene tetraol ([D10]PheT) assessed post dosing for smoked versus oral administration.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• smokers and non-smokers
• smoking at least 10 cigarettes daily for the past year (for smokers)
• in good physical health (no unstable medical condition)
• stable, good mental health (not currently, within past 6 months, experiencing unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the DSM-IV criteria).

Exclusion Criteria:

• subjects who have, within the past 6 months, experienced unstable or untreated psychiatric diagnoses, including substance abuse, as determined by the DSM-IV criteria.
• subjects using any other tobacco or nicotine products.
• female subjects who are pregnant or nursing.
• subjects with an unstable medical condition.

Contacts and Locations

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Locations

United States, Minnesota
Tobacco Use Research Center
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

University of Minnesota - Clinical and Translational Science Institute

Investigators

Principal Investigator:	Stephen S Hecht, Ph.D.	University of Minnesota Masonic Cancer Center

More Information

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Publications:

ATSDR (Agency for Toxic Substances and Disease Registry). 1990. Toxicological Profile for Polycyclic Aromatic Hydrocarbons. Acenaphthene, Acenaphthylene, Anthracene, Benzo(a)anthracene, Benzo(a)pyrene, Benzo(b)fluoranthene, Benzo(g,i,h)perylene, Benzo(k)fluoranthene, Chrysene, Dibenzo(a,h)anthracene, Fluoranthene, Fluorene, Indeno(1,2,3-c,d)pyrene, Phenanthrene, Pyrene. Prepared by Clement International Corporation, under Contract No. 205-88-0608. ATSDR/TP-90-20.

Bock, F.G. and T.L. Dao. 1961. Factors affecting the polynuclear hydrocarbon level in rat mammary glands. Cancer Res. 21: 1024-1029.

BOYLAND E, SIMS P. Metabolism of polycyclic compounds. 21. The metabolism of phenanthrene in rabbits and rats: dihydrodihydroxy compounds and related glucosiduronic acids. Biochem J. 1962 Sep;84:571-82.

BOYLAND E, WOLF G. Metabolism of polycyclic compounds. 6. Conversion of phenanthrene into dihydroxydihydrophenanthrenes. Biochem J. 1950 Jun-Jul;47(1):64-9.

Budavari, S., M.J. O'Neil and A. Smith (Eds.). 1989. The Merck Index. Merck & Co., Inc. Rahway, NJ, pp. 1143-1144.

Buening MK, Levin W, Karle JM, Yagi H, Jerina DM, Conney AH. Tumorigenicity of bay-region epoxides and other derivatives of chrysene and phenanthrene in newborn mice. Cancer Res. 1979 Dec;39(12):5063-8.

Chang, L.H. 1943. The fecal excretion of polycyclic hydrocarbons following their administration to the rat. J.. biol. Chem. 151: 93-99.

Chaturapit S, Holder GM. Studies on the hepatic microsomal metabolism of (14C) phenanthrene. Biochem Pharmacol. 1978;27(14):1865-71.

FALK HL, KOTIN P, THOMPSON S. INHIBITION OF CARCINOGENESIS. THE EFFECT OF HYDROCARBONS AND RELATED COMPOUNDS. Arch Environ Health. 1964 Aug;9:169-79.

GRANT G, ROE FJ. THE EFFECT OF PHENANTHRENE ON TUMOUR INDUCTION BY 3,4-BENZOPYRENE ADMINISTERED TO NEWLY BORN MICE. Br J Cancer. 1963 Jun;17:261-5.

HUGGINS C, YANG NC. Induction and extinction of mammary cancer. A striking effect of hydrocarbons permits analysis of mechanisms of causes and cure of breast cancer. Science. 1962 Jul 27;137(3526):257-62.

IARC (International Agency for Research and Cancer). 1983. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Polynuclear Aromatic Compounds. Part 1. Chemical Environmental and Experimental Data, Vol. 32. World Health Organization, Lyon, France, pp. 419-430.

Kennaway, E.L. 1924. On the cancer-producing tars and tar-fractions. J. Ind. Hyg. 5: 462-488.

LaVoie EJ, Tulley-Freiler L, Bedenko V, Hoffman D. Mutagenicity, tumor-initiating activity, and metabolism of methylphenanthrenes. Cancer Res. 1981 Sep;41(9 Pt 1):3441-7.

Mabey, W.R., J.H. Smith, R.T. Podoll, et al. 1982. Aquatic fate process data for organic priority pollutants. U.S. Environmental Protection Agency, Office of Water Regulations and Standards, Washington, D.C. EPA 440/4-81-014.

Nordqvist M, Thakker DR, Vyas KP, Yagi H, Levin W, Ryan DE, Thomas PE, Conney AH, Jerina DM. Metabolism of chrysene and phenanthrene to bay-region diol epoxides by rat liver enzymes. Mol Pharmacol. 1981 Jan;19(1):168-78.

Nousiainen U, Törrönen R, Hänninen O. Differential induction of various carboxylesterases by certain polycyclic aromatic hydrocarbons in the rat. Toxicology. 1984 Sep 14;32(3):243-51.

Pfeiffer, E.H. 1977. Oncogenic interaction of carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons in mice. IARC Scientific Publication No. 16. Air Pollution and Cancer in Man. International Agency for Research on Cancer, Lyon, France, pp. 69-77. (Cited in ATSDR, 1990)

Rahman A, Barrowman JA, Rahimtula A. The influence of bile on the bioavailability of polynuclear aromatic hydrocarbons from the rat intestine. Can J Physiol Pharmacol. 1986 Sep;64(9):1214-8.

ROE FJ. Effect of phenanthrene on tumour-initiation by 3,4-benzopyrene. Br J Cancer. 1962 Sep;16:503-6.

Roe, F.J.C. and G.A. Grant. 1964. Tests of pyrene and phenanthrene for incomplete carcinogenic and anticarcinogenic activity. Br. Emp. Cancer Campaign 41: 59-60. (Abstract) (Cited in IARC, 1983)

Nørager O, Town WG, Petrie JH. Analysis of the registry of toxic effects of chemical substances (RTECS) files and conversion of the data in these files for input to the environmental chemicals data and information network (ECDIN). J Chem Inf Comput Sci. 1978 Aug;18(3):134-40.

ROE FJ, SALAMAN MH. Further tests for tumour-initiating activity: N, N-di-(2-chloroethyl)-p-aminophenylbutyric acid (CB1348) as an initiator of skin tumour formation in the mouse. Br J Cancer. 1956 Jun;10(2):363-78.

Salamone, M.F. 1981. Toxicity of 41 carcinogenic analogs. Prog. Mutat. Res. 1: 682-685. (Cited in U.S. EPA, 1988)

Sax, N.I. and R.L. Lewis (Eds.). 1987. Hawley's Condensed Chemical Dictionary, 11th ed. Van Nostrand Reinhold Company, New York, p. 895.

Scribner JD. Tumor initiation by apparently noncarcinogenic polycyclic aromatic hydrocarbons. J Natl Cancer Inst. 1973 Jun;50(6):1717-9.

Simmon VF, Rosenkranz HS, Zeiger E, Poirier LA. Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host-mediated assay. J Natl Cancer Inst. 1979 Apr;62(4):911-8.

Sims P. Qualitative and quantitative studies on the metabolism of a series of aromatic hydrocarbons by rat-liver preparations. Biochem Pharmacol. 1970 Mar;19(3):795-818.

STEINER PE. Carcinogenicity of multiple chemicals simultaneously administered. Cancer Res. 1955 Oct;15(9):632-5.

Storer JS, DeLeon I, Millikan LE, Laseter JL, Griffing C. Human absorption of crude coal tar products. Arch Dermatol. 1984 Jul;120(7):874-7.

U.S. EPA (U.S. Environmental Protection Agency). 1987. Health and Environmental Effects Profile for Phenanthrene. Prepared by the Environmental Criteria and Assessment Office, Office of Health

Responsible Party:	University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:	NCT01092650 History of Changes
Other Study ID Numbers:	0707M13481
First Posted:	March 25, 2010
Last Update Posted:	October 27, 2014
Last Verified:	October 2014

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:

Tobacco toxicants; Polycyclic aromatic hydrocarbons; Smoking