Biomedical subjects

Joni Jensen

Publications and source records attributed to Joni Jensen.

14 recordsLinked to original sources

PubMed2007

Quantitation of an acetaldehyde adduct in human leukocyte DNA and the effect of smoking cessation.

Acetaldehyde is one of the most prevalent carcinogens in cigarette smoke. It is also a major metabolite of ethanol and is found widely in the human diet and environment. Acetaldehyde DNA adducts are critical for its carcinogenic properties. The role of acetaldehyde DNA adducts in human cancer related to tobacco and alcohol exposure could be investigated with a suitable biomarker. Therefore, in this study, we have developed a method for analysis of the major DNA adduct of acetaldehyde, N2-ethylidene-dGuo (1), in human leukocyte DNA. Leukocyte DNA was subjected to enzyme hydrolysis in the presence of NaBH3CN, which converts adduct 1 to N2-ethyl-dGuo (2). [15N5]N2-ethyl-dGuo was used as the internal standard. After solid-phase extraction, N2-ethyl-dGuo was quantified by LC-ESI-MS/MS-SRM. The method was sensitive, accurate, and precise, and applicable to low microgram amounts of DNA. It was applied to investigate the effect of smoking cessation on levels of adduct 1, measured as adduct 2. Twenty-five smokers who were only light drinkers were eligible for the study. Levels of adduct 2 were quantified at two baseline time points separated by one week and again after four weeks of abstinence from smoking and alcohol consumption. The mean (+/-S.D.) levels of adduct 2 measured in the leukocytes of the smokers were 1310 +/- 1720 (range 124-7700) and 1120 +/- 1140 (range 138-5760) fmol/micromol dGuo at the two baseline points and 705 +/- 438 (range 111-1530) fmol/micromol dGuo after 4 weeks of cessation. The median level of adduct 2 decreased significantly by 28% upon quitting smoking (P = 0.02). These results demonstrate that the major acetaldehyde DNA adduct can be reliably quantified by MS/MS methods in human leukocyte DNA and that cigarette smoking has a modest but significant effect on its levels.

Acetaldehyde↗

PubMed2006

Tobacco-specific nitrosamines in new tobacco products.

New tobacco products, designed to attract consumers who are concerned about the health effects of tobacco, have been appearing on the market. Objective evaluation of these products requires, as a first step, data on their potentially toxic constituents. Tobacco-specific nitrosamines (TSNAs) are an important class of carcinogens in tobacco products, but virtually no data were available on their levels in these products. In the present study, we analyzed several new products-Ariva, Stonewall, Exalt, Revel, Smokey Mountain, and Quest-for TSNAs and compared their TSNA levels with those in nicotine replacement products and conventional smokeless tobacco and cigarette brands. TSNAs were not detected in Smokey Mountain, which is a tobacco-free snuff product. The lowest levels among the new products containing tobacco were in Ariva and Stonewall (0.26-0.28 microg/g wet weight of product). The highest levels in the new products were found in Exalt (3.3 microg/g tobacco), whereas Revel and Quest had intermediate amounts. Only trace amounts were found in nicotine replacement products, and conventional brands had levels consistent with those reported in the literature. These results demonstrate that TSNA levels in new tobacco products range from relatively low to comparable with those found in some conventional brands.

Carcinogenicity Tests↗

PubMed2006

Comparison of polymorphisms in genes involved in polycyclic aromatic hydrocarbon metabolism with urinary phenanthrene metabolite ratios in smokers.

The hypothesis that interindividual differences among smokers in the metabolism of polycyclic aromatic hydrocarbons (PAH) are related to lung cancer risk has been extensively investigated in the literature. These studies have compared lung cancer risk in groups of smokers with or without polymorphisms in genes involved in PAH metabolism. We believe that carcinogen metabolite phenotyping, involving the actual measurement of PAH metabolites, would be a better way to investigate differences in lung cancer risk. With this goal in mind, we have developed methods for quantifying phenanthrene metabolites in urine. Phenanthrene is the simplest PAH with a bay region, a feature closely associated with carcinogenicity. The urinary metabolite r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) is a measure of metabolic activation, whereas phenanthrols (HOPhe) are a measure of detoxification. In this study, we quantified urinary PheT/HOPhe ratios in 346 smokers who were also genotyped for 11 polymorphisms in genes involved in PAH metabolism: CYP1A1MspI, CYP1A1I462V, CYP1B1R48G, CYP1B1A119S, CYP1B1L432V, CYP1B1N453S, EPHX1Y113H, EPHX1H139R, GSTP1I105V, GSTP1A114V, and GSTM1 null. The geometric mean molar PheT/3-HOPhe ratio was 4.08 (95% confidence interval, 3.79-4.39). Ten percent of the smokers had PheT/3-HOPhe ratios of > or =9.90. We found a significant association between the presence of the CYP1A1I462V polymorphism and high PheT/3-HOPhe ratios (P = 0.02). This effect was particularly strong in females and in combination with the GSTM1 null polymorphism. In contrast, the CYP1B1R48G and CYP1B1A119S polymorphisms were associated with significantly lower PheT/3-HOPhe ratios, particularly in Blacks. There were no consistent significant effects of any of the other polymorphisms on PheT/3-HOPhe ratios. The highest 10% of PheT/3-HOPhe ratios could not be predicted by the presence of any of the 11 polymorphisms individually or by certain combinations. The effects of the CYP1A1I462 polymorphism observed here, particularly in combination with GSTM1 null, are quite consistent with reports in the literature. However, the results of this study indicate that genotyping is not an effective way to predict PAH metabolism at least as represented by PheT/HOPhe ratios.

Adolescent↗

PubMed2006

Mass spectrometric quantitation of nicotine, cotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in human toenails.

Numerous studies have quantified total cotinine (the sum of cotinine and cotinine-N-glucuronide) and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL; the sum of NNAL and its O- and N-glucuronides (NNAL-Glucs)] in the urine and blood of smokers, smokeless tobacco users, and nonsmokers exposed to environmental tobacco smoke. Analysis of hair and nails has several advantages over blood and urine testing, such as accumulation of xenobiotics during long-term exposure, ease of collection, and indefinite stability of samples. We developed sensitive methods for quantitation of nicotine, cotinine, and NNAL in human toenails. Nicotine and cotinine were analyzed by gas chromatography-mass spectrometry-selected ion monitoring. NNAL was assayed using liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring. The detection limits of the methods were 0.01 ng/mg toenail for nicotine, 0.012 ng/mg toenail for cotinine, and 0.02 pg/mg toenail for NNAL. In 35 smokers, the mean nicotine level was 5.9 +/- 5.6 ng/mg toenail, mean cotinine was 1.6 +/- 1.3 ng/mg toenail, and mean NNAL was 0.41 +/- 0.67 pg/mg toenail. Samples collected from six nonsmokers were negative for NNAL. In smokers, NNAL correlated with cotinine (r = 0.77; P < 0.0001). The results of this study for the first time show the presence of cotinine and NNAL in human toenails. These sensitive and quantitative methods should be useful in epidemiologic studies of the role of chronic tobacco smoke exposure, including environmental tobacco smoke exposure, in human cancer.

Cotinine↗

PubMed2005

Interventions to increase use of nicotine gum: a randomized, controlled, single-blind trial.

Medication noncompliance with smoking cessation pharmacotherapies is a significant problem in both research and clinical settings. This randomized, controlled, single-blind study compared three single-session psychological interventions to increase use of nicotine gum during a 15-day treatment period. A total of 97 adult smokers were randomized to receive standard treatment (ST, n = 31), brief feedback (BF, n = 32) plus ST, or contingency management (CM; i.e., payment for chewing at least 12 pieces/day on 10 of 15 intervention days, n = 34) plus ST and BF. Only the CM condition led to significantly greater average daily gum use (pieces/day: ST, 6.17; BF, 7.81; CM, 10.17 [p values <.05]) and higher rates of compliance (ST, 13.6%; BF, 25.2%; CM, 65.6% [p values <.001]). No differences were observed in smoking abstinence, nicotine withdrawal, or urinary cotinine as a function of treatment. Implications of the present findings are discussed, including application to clinical trials and extension to real-world use of nicotine gum.

Adult↗

PubMed2005

Similar uptake of lung carcinogens by smokers of regular, light, and ultralight cigarettes.

Cigarette design has changed markedly over the past 60 years and sales-weighed levels of tar and nicotine have decreased. Currently, cigarettes are classified as regular (>14.5 mg tar), light (>6.5-14.5 mg tar), and ultralight (< or =6.5 mg tar), based on a Federal Trade Commission-specified machine-smoking protocol. Epidemiologic studies suggest that there is no difference in lung cancer risk among people who smoke light or ultralight cigarettes compared with regular cigarettes, but the uptake of lung carcinogens in smokers of these types of cigarettes has never been reported. We recruited 175 smokers, who filled out a tobacco use questionnaire in which their current brand was identified as regular, light, or ultralight. Urine samples were collected and analyzed for 1-hydroxypyrene (1-HOP), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides) and total cotinine (cotinine plus its glucuronides). 1-HOP and total NNAL are biomarkers of uptake of polycyclic aromatic hydrocarbons and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, lung carcinogens in cigarette smoke. Total cotinine is a biomarker of nicotine uptake. There were no statistically significant differences in urinary levels of 1-HOP, total NNAL, and total cotinine in smokers of regular, light, and ultralight cigarettes, whether the results were expressed per mg urinary creatinine, per mL of urine, or per mg creatinine divided by cigarettes per day. Levels of machine measured tar were available for the cigarettes smoked by 149 of the subjects. There was no correlation between levels of tar and any of the biomarkers. These results indicate that lung carcinogen and nicotine uptake, as measured by urinary 1-HOP, total NNAL, and total cotinine is the same in smokers of regular, light, and ultralight cigarettes. The results are consistent with epidemiologic studies that show no difference in lung cancer risk in smokers of these cigarettes.

Adult↗

PubMed2005

Longitudinal study of urinary phenanthrene metabolite ratios: effect of smoking on the diol epoxide pathway.

We have proposed that urinary phenanthrene metabolites could be used in a carcinogen metabolite phenotyping approach to identify individuals who may be susceptible to cancer induction by polycyclic aromatic hydrocarbons (PAH). In support of this proposal, we have developed methods for quantitation of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and phenanthrols (HOPhe) in human urine. PheT is the end product of the diol epoxide metabolic activation pathway of PAH, whereas HOPhe are considered as detoxification products. In this study, we investigated the longitudinal consistency of these metabolites over time in smokers and nonsmokers and compared their levels. Twelve smokers and 10 nonsmokers provided urine samples daily for 7 days, then weekly for 6 weeks. Levels of PheT, HOPhe, and PheT/HOPhe ratios were relatively constant in most individuals, with mean coefficients of variation ranging from 29.3% to 45.7%. There were no significant changes over time in levels of the metabolites or in ratios. These results indicate that a single urine sample should be sufficient when comparing phenanthrene metabolites in different groups. PheT/HOPhe ratios were significantly higher in smokers than in nonsmokers, showing that smoking induces the diol epoxide metabolic activation pathway of phenanthrene. This finding is consistent with previous studies indicating that inducibility of PAH metabolism contributes to cancer risk in smokers.

Adult↗

PubMed2005

Effects of cigarette reduction on cardiovascular risk factors and subjective measures.

STUDY OBJECTIVES: To assess the effect of continued smoking and smoking reduction on cardiovascular biomarkers (eg, WBC count, cholesterol concentrations, BP, heart rate). DESIGN, SETTING, AND PARTICIPANTS: This study, conducted at the University of Minnesota, randomized smokers interested in significantly reducing cigarette use but not quitting to either start 12 weeks of smoking reduction immediately (n = 102), assisted by nicotine replacement therapy, or to a 6-week wait list (n = 49). Those starting smoking reduction were required to reduce smoking by 25% for 2 weeks, 50% for 2 weeks, and 75% during the final 2 weeks. After 6 weeks, the subjects were asked to maintain a 50% reduction or quit. Nicotine gum and, if necessary, nicotine patch were used to achieve reduction goals. The wait list group (n = 49) smoked ad libitum for 6 weeks and then reduced smoking as previously described. MEASUREMENTS AND RESULTS: Cardiovascular biomarkers (eg, WBC count, cholesterol concentrations, BP, heart rate) were assessed at several time points after enrollment. During ad libitum smoking, cardiovascular biomarkers remained relatively stable with correlation coefficients across the various time measurements, ranging from 0.44 to 1.00 (p < 0.01 for all measures). Among successful nonabstinent reducers (64 of 151 subjects), significant improvements were found in many biomarkers (eg, hemoglobin, hematocrit, RBC and WBC counts, lipids, BP, heart rate, respiratory symptoms, all p < 0.0167). CONCLUSIONS: These results show the availability of reliable and dose-sensitive biomarkers and that reduction in smoking can lead to significant but only modest changes in cardiovascular risk factors in healthy smokers. It is not known whether the reductions in cardiovascular risk factors observed after smoking reduction are also associated with reduced disease risk. Additional research is necessary to address this issue.

Adolescent↗

PubMed2004

Effects of reduced cigarette smoking on the uptake of a tobacco-specific lung carcinogen.

BACKGROUND: Limited data are available on carcinogen uptake in smokers who reduce their smoking. To determine whether reducing the number of cigarettes smoked per day would lead to a corresponding reduction in carcinogen uptake, we measured levels of metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the urine of smokers who reduced their smoking for up to 26 weeks. METHODS: We recruited 153 smokers, of whom 151 were randomly assigned to a reduction group or a waitlist group. In the reduction group of 102 smokers, we measured the metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Gluc) at two baseline times and at weeks 4, 6, 8, 12, and 26 after baseline. Smokers were then expected to reduce their number of cigarettes per day by 25% in weeks 0-2, 50% in weeks 2-4, and 75% in weeks 4-6 and to maintain the reduced level through week 26. In the waitlist group of 49 smokers, four baseline measurements over 7 weeks were made to assess the longitudinal stability of the metabolite measurements, and then the smokers began the reduction program. All statistical tests were two-sided. RESULTS: For waitlist and reduction groups results were comparable. Statistically significant reductions in the lung carcinogen metabolites were observed at most intervals as smokers reduced the number of cigarettes smoked each day. However, the observed decreases were generally modest, always proportionally less than the reductions in cigarettes smoked per day, and sometimes transient. For example, among the 65 individuals in the reduction group who reduced cigarettes per day by 40% or more during weeks 4-12 after baseline, mean decreases in cigarettes per day were 53% (week 4), 74% (week 6), 75% (week 8), and 74% (week 12); whereas the corresponding mean reductions in NNAL plus NNAL-Gluc were 29%, 33%, 37%, and 29%. (P<.001 for all NNAL plus NNAL-Gluc values) CONCLUSIONS: Statistically significant reductions in levels of urinary metabolites of a tobacco-specific lung carcinogen were achieved by reduction in smoking, but for most smokers, reductions were modest and transient.

Adult↗

PubMed2004

Effects of reduced cigarette smoking on levels of 1-hydroxypyrene in urine.

We investigated the effects of smoking fewer cigarettes/day (CPD) on urinary levels of 1-hydroxypyrene (1-HOP), a biomarker of carcinogenic polycyclic aromatic hydrocarbon (PAH) uptake. We randomly assigned 151 smokers to either a reduction group or a waitlist group. In the reduction group, we measured urinary 1-HOP at two baseline intervals. Then, the smokers were expected to reduce their CPD by 25% in weeks 0-2, 50% in weeks 2-4, and 75% in weeks 4-6 and to maintain reduced smoking through week 26. In the waitlist group, four baseline measurements were taken and then the smokers joined the reduction group. Urinary 1-HOP was quantified at weeks 4, 6, 8, 12, and 26 after baseline. Statistically significant reductions in urinary 1-HOP were observed at most time points examined in groups of smokers who reduced to different extents. Reductions in the waitlist group were also generally significantly greater than baseline levels. The reductions in 1-HOP were usually modest (ranging from 14% to 35% in all groups and time points examined), which partially reflects the fact that there are sources of pyrene exposure other than cigarette smoke. Thus, cessation of smoking would only be expected to result in partial reductions of 1-HOP. The observed reductions in 1-HOP were not fully consistent with reductions in CPD probably due to uncontrolled dietary factors. Collectively, the results demonstrate that some smokers can achieve substantial reductions in 1-HOP, reflecting reduced uptake of polycyclic aromatic hydrocarbons, by reducing CPD, but there was not a consistent relationship between these parameters.

Adolescent↗

PubMed2004

A comparison of urinary biomarkers of tobacco and carcinogen exposure in smokers.

Recently, several potential harm reduction strategies, such as reduction in the number of cigarettes smoked and the use of modified cigarette products, have been discussed as possible means by which to reduce tobacco-related disease. To assess any potential reduction in harm by either of these approaches requires an accurate assessment of tobacco toxin exposure. We have recently completed a cigarette reduction study in which smokers were required to reduce the number of cigarettes smoked by 75%. This reduction took place over a 6-week period. We report here the comparison of urinary concentrations of tobacco alkaloid and tobacco carcinogen biomarkers in a subset of these same smokers during a 7-week period prior to any reduction in cigarette consumption. Urine samples were collected at four time points and analyzed for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and its glucuronide, 1-hydroxypyrene, anatabine, free nicotine, total nicotine (free plus glucuronidated), free cotinine, total cotinine (free plus glucuronidated), and total trans-3'-hydroxycotinine (free plus glucuronidated). Anatabine is a minor alkaloid that may be useful in assessing tobacco exposure in individuals using nicotine replacement therapies. Urinary anatabine levels were well correlated (P < 0.0001) with both free and total nicotine (r = 0.753 and 0.773, respectively). Anatabine levels were also correlated with free cotinine (r = 0.465; P < 0.001), total cotinine (r = 0.514; P < 0.001), and total NNAL (r = 0.633; P < 0.001). These data support the role of anatabine as a biomarker of tobacco exposure. 1-Hydroxypyrene is a biomarker of polycyclic aromatic hydrocarbon exposure, but unlike NNAL it is not tobacco specific. Whereas urinary concentrations of 1-hydroxypyrene were consistent across the four visits, the levels were not correlated with NNAL, anatabine, nicotine, or any nicotine metabolites.

Adult↗

PubMed2003

Preliminary study on reducing oral moist snuff use.

BACKGROUND: Tobacco exposure reduction may be an alternative treatment approach for those tobacco users who are unwilling or unable to quit tobacco use. However, very little information is available on the feasibility of this type of intervention, especially in the area of oral moist snuff tobacco (ST). This pilot study examined whether reducing ST use using various methods can be achieved and whether this reduction results in lower exposure to carcinogens. METHODS: Moist snuff users (N=40 males) were randomly assigned to 4 mg nicotine gum, non-tobacco mint snuff, brand switching, or elimination of ST use in specific situations. These approaches were used to reduce ST use or nicotine exposure by at least 25% for the first 2 weeks and 50% the subsequent 6 weeks of treatment. Follow-up sessions occurred at 12 and 26 weeks. RESULTS: Significant reductions were observed in tins per week and cotinine levels across all conditions. Among the intent-to-treat population, the abstinence rate was 15% at 26 weeks. Reduction in nicotine exposure was associated with reduction in exposure to nitrosamines. CONCLUSION: Reduction in ST use may be a viable approach for those oral moist ST users with no immediate quit plans. Future research in this area is needed.

Administration, Oral↗

PubMed2003

Lack of effect of 5HT3 antagonist in mediating subjective and behavioral responses to cotinine.

Previous studies have shown that cotinine, a metabolite of nicotine, may antagonize some of the therapeutic effects of nicotine. The mechanisms underlying cotinine's effects are unclear, but cotinine has been observed to increase serotonin levels in the brain. Thus, it is possible that blocking serotonin effects may antagonize the actions of cotinine, thereby reducing its impact on responses to nicotine. This study determined whether granisetron, a 5HT(3) receptor antagonist, would enhance the efficacy of the nicotine patch. Subjects were randomly assigned to one of the three granisetron conditions (N=43 for 2 mg/day; N=43 for 1 mg/day; N=42 for 0 mg/day) and asked to take the assigned medication daily during 15 days of tobacco abstinence. Because we were interested in interactions between cotinine and serotonin, all groups were also treated with a 21-mg nicotine patch. Assessments of withdrawal symptoms were made for 1 week during baseline smoking and several times during the experimental period. There was a near but nonsignificant difference among groups on a measure of tobacco withdrawal and no significant differences on global measures of drug effects or physiological measures. The data do not strongly support the hypothesis that 5HT(3) agonism is the mechanism by which cotinine offsets the effects of nicotine.

Administration, Cutaneous↗

PubMed2003

Efficacy of nicotine patch in smokers with a history of alcoholism.

BACKGROUND: Smokers with a history of alcohol dependence may have more difficulty quitting, might relapse to alcohol use, and might especially benefit from nicotine replacement therapy for smoking cessation. METHODS: One hundred fifteen smokers with a history of alcohol dependence (median of 5 years previously) were randomly assigned to either a 21-mg nicotine patch or placebo in a trial designed to be as similar as possible to a prior study that examined smokers with no history of alcoholism. Both studies were of heavy smokers with similar levels of nicotine dependence; thus, any differences in trials would be due to a history of alcohol problems per se. RESULTS: In the current trial, adjusted prolonged smoking abstinence in those with a history of alcohol dependence was higher in the active than the placebo group at end-of-treatment (28% vs. 11%; odds ratio, 3.2; p = 0.04) and at 6-month follow-up (24% vs. 6%; odds ratio, 4.9; p = 0.02). Among subjects not lost to follow-up, none reported drinking problems or increases in craving for alcohol. Smoking abstinence was not lower and the odds ratio for nicotine patch therapy was not greater in smokers with a history of alcohol dependence than in smokers with no such history. CONCLUSIONS: Heavy smokers with a history of alcoholism benefit from nicotine patch treatment. A history of alcohol problems after a period of stable sobriety does not appear to influence smoking outcomes or response to nicotine replacement. Although no smokers relapsed to alcohol use, a trial that follows up all subjects is needed to verify this.

Administration, Cutaneous↗