Table 1.

A panel of biomarkers for investigating tobacco carcinogen and toxicant uptake and their possible relationship to cancer.

		Range of recent mean values (nmol/24h unless noted otherwisea)
Urinary biomarkers	Source	Smokers	Non-smokers	References (smokers)	References (non-smokers)
Nicotine equivalentsb	Nicotine	70.4–154 µmol/24 h	NAc	(42,52,77–81)
Total NNAL	NNK	1.1 – 2.9	NA	(16,42,52,79,81–85)
Total NNN	NNN	0.049 – 0.24	NA	(13,83,84,86)
1-HOP	Pyrene	0.50 – 1.45	0.18 – 0.50	(16,42,52,79,80,82,87,88)	(42,52,80,87,88)
MHBMA	1,3-Butadiene	15.5 – 322	0.65 – 7.5	(16,42,78,82)	(16,42,82)
SPMA	Benzene	3.2 – 32.1	0.17 – 3.14	(16,52,78–80,82,87,89)	(16,52,78,80,82,87,89)
HPMA	Acrolein	5,869 – 11,190	1,131 – 1,847	(16,42,52,78–80,82,89)	(16,42,52,78,80,82)
HBMA	Crotonaldehyde	1,965 – 26,000	242 – 3,200	(16,78,90)	(16,78,90)
HEMA	Ethylene oxide	19.1 – 102	6.51 – 38.8	(16,89)	(16,89)
Cd	Cadmium	2.3 – 12.8	1.34 – 8.04	(91–94)	(91–94)
8-epi-PGF2αd	Oxidative damage	1.48 – 2.80	0.62 – 1.13	(95–97)	(95,97)
PGE-M	Inflammation	54 – 60	31.6 – 45.3	(27,98)	(27,98)
		Recent data (pmol/g globin; mean ± S.D.)
Hemoglobin adducts	Source	Smokers	Non-smokers	References (smokers)	References (non-smokers)
Cyanoethylvaline	Acrylonitrile	112 ± 81	6.5 ± 6.4	(52,99)	(52,99)
Carbamoylethylvaline	Acrylamide	84.1 ± 41.8	27.8 ± 7.1	(52,99)	(52,99)
Hydroxyethylvaline	Ethylene oxide	132 ± 92	21.1 ± 12.7	(52,99)	(52,99)
4-Aminobiphenyl-globin	4-Aminobiphenyl	0.26 ± 0.006e	0.067 ± 0.009e	(42,99)	(42,99)
		Recent data (fmol/µmol dN; mean ± S.D.)
Leukocyte DNA adducts	Source	Smokers	Non-smokers	References (smokers)	References (non-smokers)
N6-hydroxymethyl-dAdo	Formaldehyde	179 ± 205	15.5 ± 33.8	(100)	(100)
N2-ethylidene-dGuo	Acetaldehyde	1,310 ± 1,720	705 ± 438	(101)	(101)
		Mean concentrations
Other	Source	Smokers	Non-smokers	References (smokers)	References (non-smokers)
Exhaled CO	Carbon monoxide	17.4 – 34.4 ppm	2.6 – 6.5 ppm	(34,52)	(34,52)
Carboxyhemoglobin	Carbon monoxide	3.4 – 7.1 %	0.35 – 1.45 %	(34,42,52,81)	(34,42,52,81)

^aBased on 1.3g creatinine per 24h in smokers and 1.5g creatinine per 24h in non-smokers, or 1.5 l urine per 24h. Creatinine determinations were mainly by a modified Jaffe reaction using a certified automated clinical analyzer.

^bAbbreviations

nicotine equivalents, the sum of nicotine, cotinine, 3'-hydroxycotinine, and their glucuronides;

total NNAL, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides;

total NNN, N'-nitrosonornicotine and its glucuronides;

1-HOP, 1-hydroxypyrene and its glucuronides/sulfates;

MHBMA, the sum of 1-hydroxy-2-(N-acetylcysteinyl)-3-butene and 1-(N-acetylcysteinyl)-2-hydroxy-3-butene;

SPMA, S-phenyl mercapturic acid;

HPMA, 3-hydroxypropyl mercapturic acid;

HBMA, 4-hydroxybut-2-yl mercapturic acid;

HEMA, 2-hydroxyethyl mercapturic acid;

8-epi-PFG_2α, 9,11,15-trihydroxyprosta-5,13-dien-1-oic acid;

PGE-M, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranorprostane-1,20-dioic acid

^cNA=Not applicable as these are not detected in the urine of non-smokers unless they use other tobacco products, nicotine replacement products (for nicotine equivalents, and sometimes NNN (13)), or are exposed to secondhand smoke, in which case levels are usually less than 5% of smoker levels (102,103).

^dDetermined by mass spectrometry

^eWeighted mean ± S.D.