Clinical Chemistry
303-308
42:2
U-
U-
(1996)
Effect of cigarette smoking on pentane excretion
in alveolar breath
E.
DAVID
EULER,*
SHASHANK
J.
DAVE,
and
HONGSHENG
Guo
The concentrations
of acetone,
isoprene,
and pentane
in
alveolar breath were examined
in 50 smokers and 50 nonsmokers by gas chromatography.
The baseline pentane in
smokers was 0.17 ± 0.03 nmoltL
(mean ± SE), which was
not different
from pentane
in nonsmokers
(0.23 ± 0.03
nmollL).
There were also no differences
between
smokers
[7-9] and F2-isoprostanes[10]. The increased serum concentrationsof malondialdehyde
were reduced by dietary supplements
of vitamin E [9], and the high concentrationsof F2-isoprostanes
fell significantly
(P = 0.03) after2 weeks of abstinencefrom
and nonsmokers
in the concentrations
of acetone
and
isoprene.
Serial breath samples
were obtained
from 15
smokers
before smoking
and at 5, 15, and 60 mm after
smoking.
Although
acetone
was not altered by smoking,
isoprene
increased
by 86% ± 26% 5 mm after smoking (P
<0.001)
and returned
to baseline
10 mm later. Pentane
increased by 456% ± 156% 5 mm after smoking (P <0.001)
and remained
increased
10 mm
later (204% ± 73% of
baseline, P <0.05). Isoprene
concentrations
in mainstream
cigarette
smoke were >5000
times greater
than breath
concentrations,
whereas pentane could not be detected
in
mainstream
smoke. Because pentane is produced
from the
terol and its uptake by macrophages
[ii].
Although
numerous
methods
are available for measuring
oxidative stress in human subjects, the measurement
of alkanes
smoking [10]. Chronic smoking has alsobeen shown to increase
the rate of oxidation of isolated low-density
lipoprotein
choles-
in expiredbreath isthe only noninvasivemethod [12]. Pentane
is generated
from peroxidation
of n-6 polyunsaturated
fatty
acids and the subsequent
beta-scission
of the intermediate
hydroperoxides
[13]. Pentane is only a minor reaction product,
and itsformation depends on the presence of transition-metal
ions [14]. Despite these limitations,
the use of pentane as an in
vivo marker of lipidperoxidationhas been validatedextensively
in experimental
animals [12].
Pentane excretion has been shown to be higher in smokers
than nonsmokers
[15, 16] and to be decreased in smokers by
peroxidation
of n-6 polyunsaturated
fatty acids, the results
provide evidence that cigarette
smoking causes an immediate increase in lipid peroxidation.
dietary
m1ts:
free
radicals
.
Cigarette
smoking
has been implicated
in the etiology
of
respiratory
disease, cancer, and atherosclerosis
[1-3]. Tobacco
smoke containslargenumbers of freeradicals
thatare capableof
initiating
or promoting
oxidative injury [4]. Reactive oxygen
speciesmay also be generated
in smokers by phagocytes that are
activatedin response to pulmonary inflammation [5, 6]. Several
studies have suggested thatoxidative injury may play a seminal
role in mediating the health risks associated
with cigarette
smoking [4]. Cigarette
smokers have higher lipid peroxidation
products in their blood than do nonsmokers
/7-10], and smoking increasesthe serum concentrations
of malondialdehyde
Loyola University
Medical Center, Room 0742, 2160 South 1st Ave., Maywood, IL 60153.
*Author for correspondence. Fax 708-2 16-943 3.
Received September 8, 1995; accepted November
of either
with
vitamin E [15] or beta-carotene
the measurement
of pentane
in
human breath isthe coelutionof isopreneon most chromatographic columns
[17-20].
Isoprene is also the predominant
hydrocarbon in tobacco smoke [21, 22], and the passiveincrease
lipidperoxidation. gas
chromatography. hydrocarbons. alkanes#{149}
acetone
INDEXING
supplements
[16]. A major difficulty
3, 1995.
303
of thiseffluentin the breath of smokers might be misinterpreted
as an increase in pentane. In addition to alkane formation,
lipid
peroxidation
has been shown to produce
acetone [23, 24] in
experimentalanimals.Because acetone isa major constituentof
human breath [18, 20, 25-28], conceivably
the amount of this
effluentmight change iftobacco smoke initiates
or promotes
lipid peroxidation.
The purpose of the present study was to measure acetone,
isoprene,
and pentane in the alveolar breath of smokers and
nonsmokers by injectingsingle-breathsamples directlyinto a
gas chromatograph. Serialsampling of alveolarair was performed to determine the effectsof smoking one cigaretteon the
excretionof these three effluents.
Ambient airwas analyzed to
determine the contribution of exogenous contaminants to
breath effluents.
Mainstream cigarettesmoke was alsoanalyzed
to determine the passivecontributionof tobacco combustion
products to breath effluents.
304
Euler
et al: Pentane
in alveolar
breath
of smokers
prepared for acetone (Sigma, St. Louis, MO) by diluting 100Materials and Methods
400 1iL of liquid acetone with 2000 mL of organic-free
water.
Breath samples
were collected
from 100 healthy volunteer
subjects, 50 smokers and 50 nonsmokers.
Subjects were excluded
An aliquot of each dilution (10 giL) was vaporized into 1500 mL
if they reported a history of arthritis, cirrhosis, colitis, diabetes,
of hydrocarbon-free air.The slope of the acetone calibration
or ischemic heart disease. Subjects were also excluded if they
curve was 12.5 (SE 0.05), with S = 1.3.
were taking dietarysupplements of vitamin E, vitamin C, or
The precision of the breath assay was determined
by meabeta-carotene.The nonsmokers were excluded if they reported
suringthe intra-and interassayCVs forrepeatedmeasurements
a history of chronic exposure to secondhand smoke. The
in one nonsmoker. The intraassay
CV was determined
by
smokers group included only those who smoked at least20
drawing 10 air samples (60 mL) from one breath collection bag
cigarettes per day for at least 2 years. All subjects were breathing
and was 1.8% for acetone, 2.3% for isoprene,and 13% for
smoke-free ambient airfor 1 h or more before breath sampling.
pentane. The interassayCV, determined
by collecting
10 seSerialbreath samples were obtained from 15 of the smokers,
quential alveolar air samples (750 mL) into different bags over a
alveolarairbeing sampled before and at 5, 15, and 60 mm after
10-mm interval,
was 3.5% for acetone,5.9% for isoprene,and
thesesubjectssmoked a singlecigarette.
All 15 subjectsinhaled
24% for pentane.
the smoke and smoked the cigaretteto completion.The protoWhere possible, the results were expressed as the mean ±
col was approved by the Institutional
Review Board of Loyola
SE. An unpaired f-test was used to compare group means when
University
Medical Center.
group variances were equivalent.
When an F-test showed unAlveolar air samples (750 mL) were collected with a comequal group variances, then group means were compared with a
mercially available breath collection system (Quintron,
MenoMann-Whitney
test. When the data were expressed
as the
monee Falls, WI). Preliminary
studies showed that the concenfrequency of an event or characteristic,
a Fisher’s exact test was
trations
of organic effluents
in breath were stable in these
used to make comparisons.
Repeated-measures
analysis of varimultilaminate
collection
bags for 24 h. Breath samples were
ance (ANOVA) was used to compare serialbreath samples in
aspiratedfrom the collectionbags into air-tightglasssyringes
smokers.
If the ANOVA
yielded a significant
F-value, then
(60 mL) within 5 h of breath sampling. Samples of ambient air
individual
group
means
were compared
with a Student(500 mL) were also obtained at the time of breath sampling. To
Newman-Keuls
test.
examine the organic components
in cigarette smoke, we collected mainstream
smoke in a 150-mm length of polyvinylchloResults
ridetubing (6.4mm diameter),drawing ambient airthrough a lit
Of the 50 subjects in each group, 60% of the smokers and 64%
cigarette into the tubing at a flow rate of -800 mL/min. When
of the nonsmokers were men (P = 0.20). The mean age of the
the cigarette had burned to a butt length of 10 mm (-2 mm),the
smokers was 44.7 ± 1.6 years (range,23-72) and not signifiair flow was terminated
and a smoke sample (10 mL) was
candy different from the mean age of the nonsmokers
(48.0 ±
aspiratedthrough a sideportin the tubing intoan air-tight
glass
2.3; range, 22-75). The smokers smoked an average of 22.2 ±
syringe and dilutedwith 1500 mL of hydrocarbon-freeair.A
0.7 cigarettes per day. The cumulative total of cigarettes smoked
totalof four differentfilter
cigarettebrands were tested(three
ranged from 5 to 120 pack years (mean 27.7 ± 2.7). Of the 15
cigarettes per brand). The brands were chosen on the basis of
smokers in the subgroup that had serial breath sampling, 73%
their frequency of use by the 50 smokers.
were men, ranging in age from 23 to 70 (mean 45.2 ± 4.1).This
Alveolar air, ambient air, and mainstream
cigarette
smoke
group smoked a cumulative totalof from 5 to 69 pack years
were analyzed by gas chromatography
according to previously
(mean, 29.1 ± 5.0).
published
methods [20]. We modified our original method to
Table 1 shows the concentrations
of organic effluents that
include
a 25 m X 0.53 mm Poraplot
Q
capillary
column
were
measured
in
the
breath
of
smokers
and nonsmokers.
(Chrompack,
Raritan, NJ), which had a capacity ratio of 6.0
Acetone
concentrationswere
identical
in
the
two groups of
(33 000 theoretical
plates).
Helium was used as the carriergas at
subjects.
Although
isoprene
and
pentane
tended
to be lower in
a flow rate of 10 mL/min. The temperature
of the sampling loop
smokers, the differences
did not reach statistical significance.
was ambient,
the injector
temperature
was 90 #{176}C,
and the
The concentrations
of acetone, isoprene, and pentane were also
detector temperature
was 200 #{176}C.
The column temperature
was
the passive contribution
held at 30 #{176}C
for I mm, then increased by 40 #{176}C/min
to 95 #{176}C, measured in ambient air to determine
of exogenous
effluents
to breath effluents.
The number
of
by 2.0 #{176}C/min
to 119 #{176}C,
and by 50 #{176}C/min
to 200 #{176}C
and was
ambient air samples (n = 50) was less than the total number of
held there for2 mm. A singlei-un required --30 mm.
Calibrationwas performed with a commercially available subjects in the study because breath samples were often obtained
from multiple subjectsbreathing the same ambient air.The
referencegas mixture of hydrocarbons (C2-C) at a concentraconcentrations
of acetone, isoprene, and pentane in ambient air
tion of 100 L/L
(Alltech,
Deerfield,
IL) and appropriate
were significantly
less (P <0.001) than the concentration of
dilutions.
A calibration
curve was constructed
from four pentane
theseeffluentsin the breath of both smokers and nonsmokers.
concentrations:
0 nL/L,
12.5 nL/L (0.51 nmol/L),
50 nL/L
For acetone and isoprene, a positive gradient from alveolar air to
(2.04 nmol/L), and 250 nL/L (10.2 nmolJL). The slopeof the
ambient
air was present
in 100% of smokers and 100% of
pentane calibration
curve was 16.6 (SE 0.04), with S
=
0.42.
nonsmokers.
For pentane,
80% of smokers and 90% of nonThe concentrationof isoprenewas estimatedfrom the pentane
calibrationcurve
[20, 27, 28]. A calibrationcurve
was
also
smokers had a positivealveolar-to-ambientgradient.The dif-
305
Clinical Chemistry 42, No. 2, 1996
Table 1. Organic effluents In breath, ciga rette smoke, and ambient air.
Conc, nmol/L
n
Acetone
50
14.7
50
50
14.7 ± 1.9
1.4 ± 0.108
1ainstream smoke
12
11 789 ± 9208
ND, not detected.
eP<0 0001 compared
with co ncentrations
±
Pentane
Isoprene
‘Jonsmokers
Smokers
mbient air
2.2
7.2 ± 0.5
0.23
± 0.3
6.2 ± 0.4
0.17
0.05
± 0.03
± 0.ola
0.18
± 0.038
ND
34 086 ± 32388
in smokers and nonsmokers.
rerence in the pentane gradient between the two groups was not
;igniflcant (P = 0.26).
To determine
the passive contribution
of smoke effluents to
)reath effluents in smokers, we also measured
the concentrations of acetone, isoprene, and pentane in mainstream
cigarette
;moke (Table
1). The average concentration
of acetone
in
mainstream
smoke was -800
times greater than the average
:oncentration
in alveolar
air. Isoprene
showed a 5500-fold
#{231}adient
from smoke to alveolar air. In contrast, the concentration of pentane in mainstream
smoke was below the detection
[imits of our method (0.02 nmol/L).
Figure 1 shows chromatograms
of alveolar air samples obtained from a representative
subject before and 5 mm after
;moking. This subjectwas a 33-year-oldman who had smoked
1 pack of cigarettes per day for 7 years. The retention
times of
the peaks thatwere identified
were 9.0 mm (acetone),11.6mm
isoprene),
and 12.6 mm (pentane).Comparison of the chroalatograms recorded before and after smoking shows a dramatic
ncrease in the amplitude of the pentane peak.The pentane area
ncreased from 2.0 to 13.0 (mVs). There was also an increase in
:he area of the isoprenepeak (from 137 to 157 mVs) and the
icetonepeak (from 81 to 100 mVs). Fig.lC shows a chromatoram of a sample of mainstream cigarettesmoke from the same
)rand of cigarettes smoked by this subject. The smoke sample
vas diluted 150:1 with hydrocarbon-free
air before it was
Enjected into the gas chromatograph.
The most striking feature
A
of this chromatogram
retention
time close
is the absence of any component
to where pentane
should have
with a
eluted
(arrow).The absence of a pentane peak was not due to the scale
on the ordinate,
since no pentane peak was observed even at
50-foldmagnification.
The short-term
effects of smoking
on the excretion of
volatileorganic compounds in alveolarairare summarized in
Fig. 2. The alveolarconcentration of acetone 5 mm after
smoking (13.2 ± 1.7 nmol/L)
was not significantly
different
from baseline (12.6 ± 2.0 nmol/L). Similar acetone concentrations were also measured at 15 and 60 mm after smoking.
In
contrast to acetone, the alveolarconcentration of isoprene
increased from 6.5 ± 0.84 to 10.3 ± 1.1 nmol/L
5 mm after
smoking. This represented
a relative increase in isoprene concentration
of 86% ± 26% (P < 0.001). Isoprene returned
to
baseline values 15 mm after smoking and showed no further
changes at 60 mm. Compared
with the brief changes in isoprene
excretion, the effect of smoking on pentane excretion was more
prolonged. Five minutes after smoking,
the concentration of
pentane in alveolar air increased from 0.23 ± 0.06 to 0.96 ±
0.24 nmol/L. This represented
a relative increase in pentane of
456% ± 198% (P <0.001). Despite a partial return towards
baseline 15 mm after smoking, the mean pentane concentration
was still significantly
(P < 0.05) increased (0.57 ± 0.19 nmol/L).
By 60 mm
the mean pentane concentration (0.38 ± 0.16
nmol/L) was not significantly
differentfrom baseline.
12C
B
C
2
1OC
8C
6C
1
I
10
11
Retention Time (mm)
ig. 1. Chromatograms
of a breath sample obtained before smoking (A) and 5 mm after smoking
moke from the same brand of cigarettes
eaks: (11, acetone:
ID
11
Retention Time (mm)
smoked
(2), isoprene;
(3), pentane.The arrow
Retention Time(mm)
(B) in one subject and (C)
mainstream cigarette
by this subject.
in C marks the time that pentane
should have eluted
had it been present(see text).
Euler
306
16
et al:Pentane in alveolarbreath of smokers
A
12
I
II
B
I
10
*1
-J
.5
E
0
E
C
C
C)
C
C)
a
C
CC
C
0
C)
a-
.t4
2
15t
Fig. 2. The short-term
2nd
effects
3rd
-
4th
of cigarette
smoking
1st
2nd
on breath concentrations
3rd
of acetone
4th
(A), isoprene (B), and pentane (C) in 15 chronic smokers.
Breath samples were obtained before smoking (1st), 5 mm after smoking (2nd), 15 mm after smoking (3rd), and 60 mm
mean ± SE for 15 subjects. , P <0.05 vs the 1st sample, C’, P <0.001 vs the 1st sample.
Discussion
The oxidative properties
of the tar and gas phases of cigarette
smoke have been elucidated
[4]. Carbon- and oxygen-centered
radicalsare thought to form in the gas phase from the interaction of nitrogendioxide with other organic components
such as
isoprene.One puffof smoke isestimatedto contain 1017organic
free radicalsin the gas phase [4].The tar phase of cigarette
smoke contains
a quinone/semiquinone
complex,
which can
reduce oxygen to superoxideanion.The highlyreactiveradicals
from the gas and tarphasesof cigarette smoke would be exposed
initially to the alveolar surface of epithelial cells. Free radicals or
theirreactionproducts might alsodiffuse through the epithehum, interstitium,
and endothelium to peroxidizelipidsin blood
cells or serum lipoproteins.
Lipid peroxidation
may also result
from the sequestrationand activationof neutrophilsin the
pulmonary
microvasculature.
In the present study,we used the excretionof pentane in
alveolar breath as an indirect
index of lipid peroxidation.
A
limitation of our method is that for peak identification
we used
the retention time of reference standards rather than mass
spectrometry.
However, we have alsoanalyzed breath by using
a more polarcolumn (PoraplotU) to change the elutionorder
of the peaks [20, 27, 28]. Because we observed the same breath
concentrations
of acetone,
isoprene,
and pentane
with both
columns, our peak identification
is quite likely accurate.
Furthermore,
Kohimuller
and Kochen [18] have confirmed
our
peak identification
in breath by using a PoraplotU column and
mass spectrometry.
The 456% increasein pentane we observed 5 mm after
smoking suggests a profound,
sudden increase in lipid peroxidation.We waited 5 mm to sample alveolarairin order to flush
the gas-phase components of cigarettesmoke from the lungs.
The pentane concentrationspossiblywould have been even
higher if sampled while smoke was stillin the alveoli.The
enhanced lipidperoxidationappeared to lastforat least15 mm.
The absence of pentane in mainstream cigarette
smoke indicates
that the pentane was of human origin.Although pentane was
present in low amounts in ambient air, it was not detectable in
mainstream
smoke because the smoke samples were diluted with
after
smoking
(4th). Each bar represents the
hydrocarbon-free
air. The failure of tobacco combustion
to
generate pentane supports the results of Barrefors and Petersson
[21], who used gas chromatography
and mass spectrometry
to
measure the hydrocarbon
content in sidestream
and environmental tobacco smoke.
Because of the extreme reactivity of free radicals, it is not
surprising
that the increased lipid peroxidation
was temporary.
A similartransientincreasein arterial concentrations
of conjugated dienes was observed in anesthetized
rabbits exposed to
mainstream
cigarette smoke for 4 s [29]. However, in contrastto
our results,Morrow et al. [10] reported that smoking (3
cigarettes/30
mm) had no immediate
effects on plasma concentrationsof F2-isoprostanes.Perhaps the formation of F2-isoprostanes
is delayed relative to the formation
of pentane
or
conjugated
dienes.
Although smoking had rather dramatic short-term
effects on
pentane excretion,no long-term effectswere observed. This
finding conflicts with previous studies by Hoshino et al. [15] and
Hallard et al.[16], who reported that pentane excretionwas
increased by -50% in smokers. However, these previous investigationsdid not provide any chromatographic evidence of the
separation of pentane from other volatile organic components
in
breath. An important
limitation
of the use of basal pentane
concentrations
as an index of lipid peroxidation
is that pentane
undergoes significant hepatic metabolism
[30, 31]. Furthermore,
the high lipid solubility of pentane should result in large stores
of this compound
in body fat, which exchanges very slowly with
blood [19]. The sustainedincrease in plasma concentrations
of
malondialdehyde
and F2-isoprostanes
reported
previously
in
chronic smokers [7-10] may reflect differences in the formation,
distribution,
or metabolism
of these products
in comparison
with pentane.
Previous studies that analyzed cigarette smoke by gas chromatography
have shown isoprene to be the predominant
hydrocarbon
produced
during
tobacco
combustion
[21, 22]. Th
analysis of mainstream
cigarette smoke in our study confirme
these results. Despite an isoprerle concentration
in mainstrear
smoke that was 5500 times greater than the concentration
i
alveolar air, smoking caused only an 86% increase in breat
Clinical
Chemistry 42, No. 2, 1996
isoprene. As a water-insoluble
hydrocarbon,
isoprene may not
diffuse through interstitial fluid at a rate sufficient to equilibrate
with pulmonary
capillary blood. Alternatively,
studies in experimental
animals have shown that isoprene
may be partially
metabolized
before it reaches
the circulation
[32].
Studies on the role of acetone as an index of lipid peroxidation have given controversial
results. Exposure
of isolated
perfused hearts to a free-radical-generating
system caused increased acetone release [24]. Likewise, the treatment
of intact
rats with several free-radical-generating
xenobiotics
caused increased urinary excretion
of acetone [23]. However,
in vitro
studies of the iron-catalyzed
decomposition
of hinoleic hydroperoxide
showed no acetone formation,
despite formation of
hexanal and pentane [33]. Because acetone is a normal human
metabolite
produced
by spontaneous
decarboxylation
of acetoacetate, it is difficult to determine
the portion
in breath that
might be due to lipid peroxidation.
In the present
study,
smoking
had neither short- nor long-term
effects on breath
acetone. Despite an 800-fold gradient from mainstream
smoke
to alveolar
air, acetone
was not increased
5 mm after smoking.
307
9. Brown KM, MorricePC, DuthieGG. VitaminE supplementation
suppressesindexesof lipidperoxidation
and platelet
counts in
bloodofsmokers and nonsmokers butplasma lipoprotein
concentrations remain unchanged. Am J Clin Nutr 1994:60:383-7.
10. Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, et
al. Increasein circulating
productsof lipidperoxidation
(F2isoprostanes)in smokers. Smoking as a cause of oxidative
damage. N EngIJ Med 1995:332:1198-203.
11. HaratsDM, Ben-NaimM, Dabach Y,HollanderG, Stein0, SteinY.
Cigarette
smoking rendersLDL susceptible
to peroxidative
modification and enhanced metabolismby macrophages.Atherosclerosis1989:79:245-52.
12. Kneepkens CMF, Lepage G, Roy CC. The potential
of the hydrocarbonbreathtestas a measure oflipid
peroxidation.
FreeRadic
Biol Med 1994:17:127-60.
13. Frankel EN. Volatile lipid oxidation products.
14. Dumelin EE, TappelAL. Hydrocarbongases produced duringin
vitroperoxidation
of polyunsaturated
fattyacidsand decompositionof preformed hydroperoxides. Lipids 1977:12:894-900.
15. HoshinoER, Shariff
R,Van Gossum A,Allard
JP,PicahrdC, Kurian
R,ieejeebhoyKN. VitaminE suppressesincreasedlipid
peroxidation in cigarette
In summary,
we have shown that basal pentane excretion
in
smokers is similar to pentane excretion in nonsmokers.
However, the inhalation of smoke from a single cigarette is followed
by a sudden increase in the concentration
of pentane in alveolar
air, which lasts <60 mm. Because pentane was not present in
mainstream
cigarette
smoke, it was most probably
produced
endogenously
acids. These
by free radical attack on polyunsaturated
fatty
findings provide the first evidence for an immediate, smoking-induced
increase
in lipid peroxidation
in humans.
Conceivably,
the enhanced lipid peroxidation
may be modifiable
by antioxidant
interventions.
Additional
investigation
is needed
to determine
if the magnitude
of the smoking-induced
increase
in pentane has any prognostic
significance.
and its toxicological
5.
6.
7.
8.
implications.
Environ Health Perspect
smokers.
J Parenter
17.
18.
19.
20.
21.
beta-carotene
supplementationon lipid
peroxidation
inhumans.
Am J ClinNutr1994;59:884-90.
Cailleux A, Allain P. Is pentane a normal constituent
of human
breath?FreeRadicRes Commun 1993:18:323-7.
Kohlmuller D, Kochen W. Is n-pentane really an index of lipid
peroxidation in humans and animals? A methodological reevaluation. Anal Biochem 1993:210:268-76.
Springfield JR. Levitt MD. Pitfalls in the use of breath pentane
measurements toassess lipid
peroxidation.
J LipidRes 1994;35:
1497-504.
Mendis 5,SobotkaPA,EulerDE. Pentaneand isopreneinexpired
airinhumans: gas chromatographic
analysis
ofsinglebreath.Clin
Chem 1994:40:1485-8.
Barrefors
G, PeterssonG. Assessment of ambientvolatile
hydrocarbons from tobacco smoke
Chromatogr 1993;643:71-6.
1985;
64:111-26.
HoidalJR, Niewoehner DE. Cigarette-smoke-induced
phagocyte
recruitment
and metabolicalterations
inhumans and hamsters.
Am Rev RespirDis 1982:126:548-52.
RichardsGA, Theron AJ,Van Der Merwe CA, Anderson R. Spirometricabnormalities
inyoung smokers correlate
withincreased
chemilummnescenceresponsesofactivated
bloodphagocytes.
Am
Rev RespirDis 1989;139:181-7.
KalraJ,ChaudharyAK, Prasad K. Increasedproduction
ofoxygen
free radicals in cigarette smokers. Int J Exp Pathol 1991;72:1-7.
Bridges AB, Scott NA, Parry Gi, Belch JJF. Age, sex, cigarette
smoking and indices of free radical activity in healthy humans. Eur
J Med 1993;2:205-8.
Enter Nutr 1990:14:300-5.
16. HallardAP,RoyallD, KurianR,MuggliR,JeejeebhoyKN. Effects
of
References
1. Hoidal JR, Niewoehner DE. Pathogenesis of emphysema. Chest
1983;83:679-85.
2. Hammond EC. Smoking in relation
todeathratesof 1 million
men
and women. 1966 Monog 19. Washington,DC: NationalCancer
Institute,
1966;127-204.
3. Doyle iT, Dawler TR, Kannel WB, Kinch SH, Kahn HA. The
relationship
ofcigarette
smoking tocoronaryheartdisease.JAMA
1964:190:180-6.
4. Church DF, Pryor WA. Free radicalchemistryof cigarette
smoke
Prog Lipid Res
1982;22:1-33.
and from
22. Brunnemann KD, Kagan MR. Cox
vehicle
JE, Hoffmann
emissions.
J
D. Analysis
of
1,3-butadiene and other selected gas-phase components in cigarette mainstream and sidestream smoke by gas chromatographymass selective detection. Carcinogenesis 1990:11:1863-8.
23. Shara MA, Dickson PH, Bagchi D, Stohs Si. Excretion of formaldehyde, malondialdehyde, acetaldehyde and acetone in the urine
of rats in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin,
paraquat, endrin and carbon tetrachloride. i Chromatogr 1992:576:
221-3.
24. Cordis GA, Bagchi D, Maulik N, Das DK. High-performance
liquid
chromatographic
method
for the simultaneous
detection
of mal-
onaldehyde,acetaldehyde,
formaldehyde,acetoneand propionaldehyde to monitorthe oxidative
stressin heart.J Chromatogr
1994:661:181-91.
25.
Krotoszynski
B, Gabriel G, O’Neill H, Claudio PA. Characterization
of human expiredair:a promisinginvestigative
and diagnostic
technique.i ChromatogrScm1977:15:239-41.
26. Phillips
M, GreenbergJ.Method forthecollection
and analysis
of
volatile compounds
in
the
breath.
i
Chromatogr
1991:564:242-9.
27. Mendis S. Sobotka PA, Euler DE. Expiredhydrocarbonsinpatients
withacutemyocardialinfarction.
FreeRadic Res 1995:23:11722.
308
Euler
et at: Pentane
in alveolar
breath
of smokers
28. Mendis 5,SobotkaPA,EulerDE. Breathpentaneand plasma lipid
31. Allerheiligen
SRB, Ludden TM, Burk RF.The pharmacokinetics
o
peroxidesinischemicheartdisease.FreeRadicBiolMed 1995:
19:679-84.
29. Kirkland JB, Doerschuk CM, Gie R, BoskinC, Hogg JC.Changes
measured in arterial blood following a single breath of cigarette
smoke in rabbits. Life Sci 1991;49:1013-9.
30. Van Rij AM, Wade CR. The metabolism of low molecular weight
hydrocarbongases inman. FreeRadicRes Commun 1987:4:99103.
pentane,a by-product
of lipidperoxidation.
Drug Metab Dispo
1987:15:794-800.
32. DahI AR, Birnbaum LS, Bond IA, Gervasi PG. Henderson RF.Th
fate of isoprene inhaled by rats: comparison to butadiene. Toxico
AppI Pharmacol 1987;89:237-48.
33. Dillard Ci,TappelAL.Volatile
hydrocarbonand carbonylproduct
of lipid peroxidation:
a comparison
of pentane, ethane,
and acetone as in vivo indices. Lipids 1979;14:989-95.
hexana