Tobacco and Public Health - TCSC Indonesia

STEPHEN S. HECHT 105
Table 5.2 (continued) NNAL and its glucuronides (NNAL-Gluc) in urine: biomarkers of NNK
uptake
Study group Main conclusions Reference
7. 21 smokers and NNAL detected in amniotic fluid of 52.4% of (Milunsky et al. 2000)
30 non-smokers smokers and 6.7% of non-smokers, a
significant difference. NNAL levels in amniotic
fluid of smokers, 0.025 ± 0.029 pmol/ml
8. 12 smokers and NNAL and NNAL-Gluc not detected in follicular (Matthews et al. 2002)
10 non-smokers fluid
a Number and letter in parentheses represent number and gender of subjects.
ETS, environmental tobacco smoke.
in the urine of non-tobacco users unless they were exposed to ETS. Since NNAL is not
present in cigarette smoke, the origin of NNAL and NNAL-Gluc in urine is metabolism
of NNK. Most investigations to date demonstrate a correlation between NNAL
plus NNAL-Gluc and cotinine, indicating that NNAL plus NNAL-Gluc is an effective
biomarker of lung carcinogen (NNK) uptake, whereas cotinine is an effective biomarker
of nicotine uptake. The NNAL-Gluc:NNAL ratio varies at least tenfold in smokers and,
since NNAL-Gluc is a detoxification product whereas NNAL is carcinogenic, this ratio
could be a potential indicator of cancer risk (Carmella et al. 1995; Richie et al. 1997). In
human urine, (S)-NNAL-O-Gluc is the predominant diastereomer of NNAL-O-Gluc,
while (S)-NNAL is slightly in excess over (R)-NNAL (Carmella et al. 1999). (S)-NNAL
is the more tumorigenic enantiomer of NNAL in A/J mouse lung (Upadhyaya et al.
1999). NNAL and NNAL-Gluc are only slowly released from the human body after
smoking cessation, and this has been linked to particularly strong retention of
(S)-NNAL, possibly at a receptor site (Hecht et al. 1999).
Human uptake of carcinogens from ETS has been reviewed (Scherer and Richter
1997). Levels of 1-HOP and hydroxyphenanthrenes in urine are not consistently
increased by exposure to ETS, although small effects have been seen under some highexposure
conditions (Hoepfner et al. 1987; Scherer et al. 1992, 2000; van Rooij et al.
1994; Siwinska et al. 1999). All studies reported to date show significantly higher
amounts of NNAL plus NNAL-Gluc, or NNAL-Gluc, in the urine of ETS-exposed
humans than in unexposed controls (Table 5.2C, entries 1–5). In one study, uptake of
NNK was over six times higher in women who lived with smokers compared to women
who lived with nonsmokers (Anderson et al. 2001). In another investigation, widespread
uptake of NNK was demonstrated in a group of economically disadvantaged
schoolchildren (Hecht et al. 2001). As in smokers, a correlation between levels of
cotinine and NNAL plus NNAL-Gluc in urine has been consistently observed in ETSexposed
nonsmokers. The assay for NNAL and NNAL-Gluc in urine is ideally suited to
investigations of ETS exposure, for two reasons. First, it has the required sensitivity to
measure relatively low levels (typically about 0.05 pmol/ml urine). Secondly, since