IARC approaches to monitoring exposure of passive smoking

Existing information on the nature of passive smoking shows many pitfalls in ascertaining carcinogenic exposures. Two current activities of the International Agency for Research on Cancer are described: presentation of standardized monitoring methods for passive smoking; and an international study to explore biochemical measurements in relation to passive smoking history as assessed by interview.     

Interactive effect of combined exposure to glycol ethers and alcohols on toxicodynamic and toxicokinetic parameters

 Ethylene glycol monomethyl ether (EGME) exhibits testicular toxicity and ethylene glycol monobutyl ether (EGBE) is a solvent with haemolytic effects in rats. The study of the interaction of two glycol ethers (EGME and EGBE) and three alcohols (ethanol, n-propanol and n-butanol, 10 or 30 mmol/kg), orally co-administered in male rats, was carried out from a toxicodynamic and toxicokinetic point of view. Administered alone, EGME (10 mmol/kg) caused a 30- and 5-fold increase in the urinary creatine/creatinine ratio at 24 and 48 h, respectively, and 24 h urinary excretion of methoxyacetic acid was of 0.71± 0.042 mmol/24 h (mean±SE). The simultaneous administration of one of the three alcohols at either of the doses mentioned above did not significantly modify the urinary creatine/creatinine ratio (24 and 48 h), or the 24 h urinary excretion of methoxyacetic acid. Administered alone, EGBE (5 mmol/kg) caused an average decrease of 26% in the number of circulating red blood cells and a strong (250 times) increase in the level of plasma haemoglobin 4 h after treatment. Urinary excretion of butoxyacetic acid in rats treated with EGBE (1 mmol/kg) was 0.083±0.0039 mmol/24 h (mean±SE). The simultaneous injection of 30 mmol/kg alcohol (ethanol, n-propanol or n-butanol) almost totally inhibits the haemolytic effect of EGBE, and decreases the urinary excretion of butoxyacetic acid by 43–31%. A strong dose of alcohol (30 mmol/kg) decreases the haemolytic effect due to EGBE, and reduces the urinary excretion of butoxyacetic acid. In contrast, the coadministration of alcohol did not modify the testicular toxicity of EGME, or the 24 h urinary excretion of methoxyacetic acid. It is possible that competitive inhibition of alcohol dehydrogenase by alcohols results in the diversion of EGBE metabolism. Received: 3 July 1995/Accepted: 17 November 1995     

Physiological changes in pulmonary development related to passive smoking and its interaction with active smoking

The growth of pulmonary function between ages 5.5 and 25 years was determined in 1502 observations on 362 subjects from a representative population study of non-Mexican American whites in Tucson. There was an average of 8.8 years of follow-up, with a maximum of 12. The model developed was robust for follow-up of 3-7 observations (3 + years). Respiratory illnesses and smoking had the biggest negative impact on growth of forced expiratory volume in 1 s (FEV1), Vmax 50%/forced vital capacity (FVC) parental smoking and airway obstructive disease (AOD) were important also. Flow measures showed present and more persistent effects of disease and smoking than did FEV1.     

Passive and active exposure to cigarette smoke in a smoking experiment

Six volunteer female habitual smokers were exposed during a 2-wk experimental period to cigarette smoke, both actively and passively, in an exposure chamber (volume 10 m3, average air exchange rate 6.8 times/h), where the ambient carbon monoxide, particle, and aldehyde concentrations were monitored. Three of the six subjects were smoking at the time, 2 cigarettes (filtered, self-burning low tar brand) per person per hour, 30 cigarettes altogether during each of the 5-h experimental days in the chamber. Samples of blood and urine were taken from each subject after 3 nonsmoking days and after each day of active or passive smoking. Among the parameters tested, blood carboxyhemoglobin, plasma cotinine, and urinary mutagenicity were higher in samples taken after active smoking than after nonsmoking periods. Although the exposure conditions were similar for all subjects, the parameters measured showed quite high interindividual variation. Thioethers and thiocyanates were not significantly elevated in the active smoking samples; neither were there any differences during this short experimental period in the sister chromatid exchange frequencies. The only parameters showing an increasing trend after passive exposure, as compared with nonsmoking samples, were urinary mutagenicity and plasma cotinine, the main metabolite of nicotine.     

Influence of exposure to electromagnetic field on the cardiovascular system

1 We examined whether extremely low frequency electromagnetic fields (ELF-EMF) affect the basal level of cardiovascular parameters and influence of drugs acting on the sympathetic nervous system. 2 Male rats were exposed to sham control and EMF (60 Hz, 20 G) for 1 (MF-1) or 5 days (MF-5). We evaluated the alterations of blood pressure (BP), pulse pressure (PP), heart rate (HR), and the PR interval, QRS interval and QT interval on the electrocardiogram and dysrhythmic ratio in basal level and dysrhythmia induced by beta-adrenoceptor agonists. 3 In terms of the basal levels, there were no statistically significant differences among control, MF-1 and MF-5 in PR interval, QRS interval, mean BP, HR and PP. However, the QT interval, representing ventricular repolarization, was significantly reduced by MF-1 (P < 0.05). 4 (-)-Dobutamine (beta1-adrenoceptor-selective agonist)-induced tachycardia was significantly suppressed by ELF-EMF exposure in MF-1 for the increase in HR (DeltaHR), the decrease in QRS interval (DeltaQRS) and the decrease in QT (DeltaQT) interval. Adrenaline (nonselective beta-receptor agonist)-induced dysrhythmia was also significantly suppressed by ELF-EMF in MF-1 for the number of missing beats, the dysrhythmic ratio, and the increase in BP and PP. 5 These results indicated that 1-day exposure to ELF-EMF (60 Hz, 20 G) could suppress the increase in HR by affecting ventricular repolarization and may have a down-regulatory effect on responses of the cardiovascular system induced by sympathetic agonists.     

Antioxidant responses following active and passive smoking of tobacco and electronic cigarettes

Context: It has been indicated that acute active and passive tobacco cigarette smoking may cause changes on redox status balance that may result in significant pathologies. However, no study has evaluated the effects of active and passive e-cigarette smoking on redox status of consumers.

Objective: To examine the acute effects of active and passive e-cigarette and tobacco cigarette smoking on selected redox status markers.

Methods: Using a randomized single-blind crossover design, 30 participants (15 smokers and 15 nonsmokers) were exposed to three different experimental conditions. Smokers underwent a control session, an active tobacco cigarette smoking session (smoked 2 cigarettes within 30-min) and an active e-cigarette smoking session (smoked a pre-determined number of puffs within 30-min using a liquid with 11?ng/ml nicotine). Similarly, nonsmokers underwent a control session, a passive tobacco cigarette smoking session (exposure of 1?h to 23?±?1?ppm of CO in a 60?m³ environmental chamber) and a passive e-cigarette smoking session (exposure of 1?h to air enriched with pre- determined number of puffs in a 60?m³ environmental chamber). Total antioxidant capacity (TAC), catalase activity (CAT) and reduced glutathione (GSH) were assessed in participants’ blood prior to, immediately after, and 1-h post-exposure.

Results: TAC, CAT and GSH remained similar to baseline levels immediately after and 1-h-post exposure (p?>?0.05) in all trials.

Conclusions: Tobacco and e-cigarette smoking exposure do not acutely alter the response of the antioxidant system, neither under active nor passive smoking conditions. Overall, there is not distinction between tobacco and e-cigarette active and passive smoking effects on specific redox status indices.     

Psychophysiological reactions during active and passive stress coping following smoking cessation

This study investigated the effects of 9 days' smoking abstinence on psychophysiological stress reactions. The subjects were 40 female smokers; 20 of them intended to give up smoking in the course of the study, whereas the remaining 20 had no such intention. A first session was carried out before, a second and a third during days 3 and 9 of abstinence. The nonabstainers were tested at corresponding intervals. Each session consisted of a 30-min stress-coping phase with relaxation phases before and after. While performing a rapid information processing task (RIP) the subjects had to sustain electrical shocks which were, according to instructions, but not in fact, either avoidable (active coping) or not (passive coping). Generally, the active coping instruction produced greater responses to the RIP task than did the passive coping instruction for heart rate, systolic and diastolic blood pressure but not for finger pulse amplitude, thus resembling a beta-adrenergic stimulation. RIP processing rate was not affected, but the response rate (total of hits and commission errors) was greater during active than during passive coping. However, none of these stress reactions differed between abstainers and nonabstainers. On the other hand, both heart rate and the craving to smoke decreased significantly in the abstainer group across the 9 days. Thus, it is concluded that a deprivation of 1 h, 3 or 9 days has no differential effect on physiological stress reactions.     

Measuring problems in estimating the exposure to passive smoking using the excretion of cotinine

Quality control studies on cotinine measurements following low level environmental tobacco smoke (ETS) exposure are rare. The exposure to ETS was controlled and systematically changed in a series of experiments in a climatic chamber. Healthy nonsmoking volunteers were exposed to ETS simultaneously. The duration and level of exposure varied using high (8, 17 and 25 ppm CO), and low (2 and 5 ppm CO) exposure levels. The variation between radioimmunoassay (RIA) and gas chromatography (GC) was high as was the variation between the results of RIA laboratories. There was also a high within-laboratory-variation. A 1:10 dilution seems to be preferable over a 1:3 dilution. Freezing the urine samples immediately after collection led to the detection of higher cotinine values than freezing the samples 24 h after collection. Highly reliable data for cotinine were obtained when the urine samples were kept frozen immediately after collection and fractionated sampling over 48-72 h was used. Our data show that estimating low-level ETS exposure by measuring urinary cotinine is highly susceptible to uncontrolled variation and errors. Sufficiently reliable estimates of low-level ETS exposure can be made only when fractionated sampling over 48-72 h is used and when the urine samples are kept frozen just after collection.     

A comparison of active and passive smoking during pregnancy: long-term effects

Previous research has determined that maternal smoking during pregnancy is associated with negative effects for the child at birth and throughout childhood. Much less is known about the consequences of exposure to secondary smoke during fetal development. The present study investigates and compares the long-term consequences of active and passive smoking during pregnancy. Ninety-one children between the ages of six and nine years were tested using a comprehensive neuropsychological test battery. After considering potential confounds, children of nonsmoking mothers generally were found to perform better than the two smoking groups on tests of speech and language skills, intelligence, visual/spatial abilities and on the mother's rating of behavior. The performance of children of passive smokers was found, in most areas, to be between that of the active smoking and nonsmoking groups. It was concluded that there is a continuum of long-term smoking effects and that, although active maternal smoking is associated with effects of greater breadth and magnitude than passive maternal smoking, children of passive smokers are also at risk for a pattern of negative developmental outcomes.     

Breast cancer, passive and active cigarette smoking and N-acetyltransferase 2 genotype

The relationship of breast cancer to cigarette smoking is inconsistent in the literature, possibly due in part to heterogeneity in carcinogen metabolism. N-acetyltransferase 2 (NAT2) enzyme activity is believed to play a role in the activation of tobacco smoke carcinogens. We examined the effect of NAT2 genetic polymorphisms on risk of breast cancer from active and passive smoking. Women were recruited from those who had suspicious breast masses detected clinically and/or mammographically. Questionnaire data were collected prior to biopsy diagnosis to blind subjects and interviewers. Histopathology showed 113 cases with mammary carcinoma (30 carcinoma in situ) and 278 controls with benign breast disease. NAT2 genotype was determined using allele-specific polymerase chain reaction amplification to detect slow acetylator mutations. Effects of passive and active tobacco smoke and of NAT2 genotype on breast cancer risk were examined with logistic regression controlling for known risk factors. Models first included all controls, and subsequently 107 with no or low risk (normal breast or no hyperplasia), and finally 148 with high risk (hyperplasia, atypical hyperplasia, complex fibroadenomas). Referents had no active or passive smoke exposure. We found no association between breast cancer risk and NAT2, smoking status (never, former, current), smoking duration, or cigarettes per day. There were no effects of passive exposure among never-smokers. Models were unchanged across control groups. There were no statistical interactions between tobacco smoke exposure and NAT2. The results were similar when restricting the analysis to invasive cancers. These findings do not support the hypothesis that NAT2 is a risk factor for breast cancer or that it alters susceptibility to tobacco smoke.     

The effect of long-term repeated exposure to 3,4-methylenedioxymethamphetamine on cardiovascular and thermoregulatory changes

Rationale  3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) disrupts thermoregulation in rats and can lead to life-threatening hyperthermia in humans. MDMA administration can also lead to long-term neurotoxicity in animals and possibly humans. Objectives  The purpose of the current study was to extend previous results on the acute effects of MDMA on behavioral thermoregulation to a repeated dosing regime, simulating regular weekend use of ecstasy, on measures of thermoregulation and heart rate (HR). Materials and methods  Sprague–Dawley rats with telemetry implants were administered 40 μmol/kg MDMA on three consecutive days each week for 1 or 6 weeks before being confined to an elevated ambient temperature (T _A) (HOT; 30 ± 1°C) or an area at room temperature (ROOM; 21.5 ± 1.5°C) for 30 min. After the final drug administration, rats were placed in a thermal gradient for 4 h to allow behavioral thermoregulation. Results  HOT rats showed higher core temperature (T _C), HR, and locomotor activity than ROOM rats during confinement to a set T _A (P < 0.001). HR responses to MDMA over 6 weeks at both T _As progressively decreased with repeated dosing (P < 0.05). T _C was significantly higher in both 6-week groups compared to the 1-week groups (P < 0.05) at the end of time in the gradient. Cortical concentrations of dihydroxyphenylacetic acid (DOPAC; P < 0.05) and 5-hydroxyindole acetic acid (5-HIAA; P < 0.001) decreased significantly irrespective of T _A, while concentrations of dopamine and 5-HT did not change. Conclusion  Long-term treatment with MDMA resulted in apparent tolerance to the effects of the drug on HR, dysregulation of T _C in thermal gradient, and depletion of cortical DOPAC and 5-HIAA.     

The impact of active and passive peer influence on young adult smoking: an experimental study

Background

Peers influence adolescent and young adult smoking, but little is known about the underlying mechanisms. It is necessary to understand whether the current assumption of peer pressure is valid, or whether an alternative explanation as imitation is more appropriate. We examined whether passive (imitation) and/or active (pressure) peer influence affects young adult smoking.

Methods

An experiment was conducted among 68 daily-smoking students aged 16–24. The actual study aim was masked. Participants had to do a 30-min music task with a confederate. The experiment consisted of a 2 (smoking condition: confederate smokes or not) by 2 (pressure condition: confederate offers the participant a cigarette or not) factorial design, resulting in four conditions: (1) no smoking and no pressure (N = 15); (2) smoking but no pressure (N = 16); (3) pressure but no smoking (N = 20); and (4) smoking and pressure (N = 17). The primary outcome tested was the total number of cigarettes smoked during this music assignment.

Results

Peer smoking significantly predicted the total number of cigarettes smoked by young adults while peer pressure did not. The interaction effect of peer pressure and peer smoking was not significant.

Conclusions

Peer pressure did not have a significant additional contribution, over and above smoking of the peer. Passive (imitation) peer influence affected young adult smoking rather than active (pressure) peer influence. Thus, smoking cessation efforts should aim at preventing interaction with smoking peers and raising awareness about its impact.     

Clastogenic effect of passive smoking on bone marrow polychromatic erythrocytes of NMRI mice

The genotoxic effect of passive inhalation of sidestream cigarette smoke on bone marrow polychromatic erythrocytes was studied using male NMRI mice. The animals were placed in individual 145.2-dm3 glass chambers resembling a room provided with normal air flow. They were exposed to the sidestream smoke of a commercial brand of cigarettes smoked by a smoking machine under standard conditions. Increased formation of micronuclei within polychromatic erythrocytes (PCEs) of femoral bone marrow 30 h after passive smoking was regarded as being due to the clastogenic effect of the smoke. Passive inhalation of the diluted sidestream smoke of a single cigarette resulted in a significant increase (P less than 0.01) in the frequency of micronucleated PCEs. This clastogenic activity was found to be dose-dependent.     

Nicotine exposure can be detected in cerebrospinal fluid of active and passive smokers

A simple, rapid and sensitive liquid chromatography/mass spectrometry (LC/MS) method has been utilized for the quantitative determination of nicotine and its major metabolite cotinine (COT) in human cerebrospinal fluid (CSF) of active and passive smokers. CSF samples from 18 smokers, 15 non-smokers, 15 children, 15 infants, and 9 neonatal were analyzed for nicotine (NIC) and cotinine content. Cotinine levels in the CSF of smokers ranged from 27.3 to 457.1 ng/ml, whereas nicotine levels were considerably lower (6.0–215.1 ng/ml). Cotinine could be detected in 4 of the 15 CSF samples from non-smokers (3.5–30.4 ng/ml), and a few other passive smokers, including neonates from smoking mothers (15.6–81.1 ng/ml). The concentrations of cotinine in CSF samples suggests that nicotine easily passes into the CSF, which makes it an excellent CSF marker for tobacco-smoke exposure.     

The effect of α-amanitin on passive and active avoidance acquisition in mice

-Amanitin, a specific and potent inhibitor of form II DNA-dependent RNA polymerase, produced greater than 98% inhibition of the enzyme in mouse brain within 2 h of intracerebroventricular (icv.) injection. Mice were given one trial passive avoidance training and retested on the task 4 h later. Mice treated with -amanitin 2 h before training or immediately after training demonstrated a retention deficit when compared to non-injected or saline injected controls.Active avoidance was trained for 1 h using a Sidman schedule with a drumturning response. Performance during the last 15 min of training was compared to performance in the first 15 min of a retesting session, 4 h after training. -Amanitin, 2 h prior to training reduced the number of responses, per cent escapes and per cent avoidances in the retesting session. Post-training injection of -amanitin significantly reduced the number of responses and per cent avoidances.Rotarod and spontaneous motor activity were not affected by -amanitin. Whole body temperature was slightly and transiently reduced in icv. administration of -amanitin.     

Nicotine effect on cardiovascular system and ion channels

Smoking is a leading cause of cardiovascular disease, hypertension, myocardial infarction, and stroke. Nicotine is one of the components of cigarette smoke. Nicotine effects on the cardiovascular system reflect the activity of the nicotine receptors centrally and on peripheral autonomic ganglia. It has been found that cigarette smoke extract-induced contraction of porcine coronary arteries is related to superoxide anion-mediated degradation of nitric oxide. Treatment of rabbit aortas with an oxygen free radicals scavenger attenuated cigarette smoke impairment of arterial relaxation. Treatment of smokers with vitamin C, an antioxidant, improved impaired endothelium-dependent reactivity of large peripheral arteries. Thus it appears that chronic smoking and acute exposure to cigarette smoke extract may alter endothelium-dependent reactivity via the production of oxygen derived free radicals. This review discusses the effects of nicotine on resistance arterioles, compliance arteries, smooth muscle cells, and ion channels in the cardiovascular system. We discuss studies performed on humans, nicotine-exposed animals, and cell cultures yielding varying and inconsistent results that may be due to differences in experimental design, species, and the dose of exposure. Nicotine exposure appears to induce a combination of free radical production, vascular wall adhesion, and a reduction of fibrinolytic activity in the plasma.