We report that overall air cleaner use was marginally associated with DNA adduct levels regardless of the child’s race or sex. This finding is interesting particularly since it was independent of whether or not the air cleaner contained an active HEPA unit. There are at least two potential explanations for these data. It could be that the majority of carcinogens in ETS that can be detected in blood lymphocytes are not bound to particles but remain in the vapor phase. Vapor phase carcinogens would not be filtered by the HEPA filters in the units. This possibility is consistent with our finding that the air levels of nicotine, a vapor phase material, did not vary by air cleaner usage or type. Prior studies have demonstrated an association between housing size and ventilation, and other markers of tobacco smoke exposure (Henschen et al. 1997
; Wilson et al. 2005
). However, there is another plausible explanation. It is possible that since the air cleaners had to be turned off and on by the parent that increased time of air cleaner usage may also be surrogate indicator of unmeasured behavior changes within the family that resulted in lower exposure to ETS among the children.
While we confirmed racial differences in both hair and serum cotinine, we did not
find significant racial differences in DNA adducts. The absence of a difference in DNA adducts was surprising, given that African American children were exposed to marginally higher levels of ETS compared to White children and used their air cleaners less. Our results differ from other studies that have reported racial differences in DNA adducts. In Weiserbs’ cohort study, the authors reported that African American smokers had WBC DNA adduct levels that exceeded both White and Hispanic smokers by twofold, even after accounting for current smoking levels and lifetime tobacco use (Weiserbs et al. 2003
). Wang et al. also reported striking racial differences in DNA adducts in a cohort of non-smoking women, but in the opposite direction (Wang et al. 2008
). The authors recruited subjects from New York City (primarily African American and Dominican) and Krakow Poland (European) and tested for racial differences in DNA adducts. DNA adducts in European women exceeded those of African American women by twofold. However, exposure to air pollution was substantially higher among European women compared to African American women. In contrast, another study reported no racial difference in DNA adducts among smokers. In a case–control study of African American and Mexican American lung cancer patients, Vulimiri et al. found striking racial differences in DNA adducts among cancer patients (Vulimiri et al. 2000
). Mexican American subjects (n
= 37) had aromatic DNA adduct levels that were 38% higher than African American subjects (n
= 6), but there were no significant racial differences in DNA adduct levels among the control subjects.
The absence of a racial differences in DNA adducts in this cohort is surprising. It has been documented in previous studies that African American smokers suffer higher rates of lung cancer when compared with White smokers, despite lower reported levels of tobacco use (United States Department of Heath and Human Services 1998
; United States, Public Health Service, Office of the Surgeon General 2006
). Certainly, Haiman et al. demonstrated higher lung cancer rates among African Americans compared with all other racial and ethnic groups (Haiman et al. 2006
). This phenomenon has also been observed among lifetime non-smokers. Data from the Cancer Prevention Study II Cohort identified an increased risk of lung cancer mortality among African American women when compared with White women (HR = 1.43, CI = 1.11–1.85) (Thun et al. 2006
). Given that DNA adducts are associated with the development of lung tumors, it is plausible that African Americans would have higher adduct levels (Tang et al. 2001
; Peluso et al. 2005
). However, our data do not support this hypothesis. There are some possible explanations for our findings. First, we measured adducts in a surrogate tissue (WBCs) rather than the target tissue (lung). Thus, the WBC DNA adducts may not represent the aggregate amount of tobacco-induced damage occurring in the lungs. Moreover, WBCs may represent a surrogate for other exposures in adults that are not experienced by children, to the same extent. Thus, these exposures could be associated with a smoking lifestyle. In addition, our cohort consisted solely of non-smoking children; studies of racial differences in lung cancer have focused primarily on smoking adults, and may be racial differences in DNA adducts occur only among active smokers. Lastly, the absence of racial differences in 1-Hydroxypyrene could indicate that there may have been unmeasured sources of PACs in our study.
Our results are subject to some limitations. First, our study was cross-sectional in design. At best, we could only identify an association between adducts and tobacco smoke exposure. Second, air nicotine levels were only measured in the main activity room of the home. Thus, there may have been unmeasured exposures in other parts of the home or outside of the home that contributed to adduct formation. Thus, parents may have smoked around their child in other parts of the home that would not have been captured by the nicotine dosimeter. In addition, we were unable to determine the impact of the air cleaners on PACs—compounds likely leading to adduct formation—as airborne levels of these compounds were not directly measured. Unfortunately, urine 1-HP levels cannot differentiate inhaled versus ingested exposure to PACs, and 1-HP levels reflect only recent exposure to PAC materials. While we did measure serum and hair cotinine levels that would capture ETS exposures outside of the home, it is well known that these biomarkers differ significantly by race. Still, we did not find any association of WBC DNA adducts with serum cotinine or hair cotinine—which operate as aggregate biomarkers of exposure. Third, we only measured PAC-DNA adducts, which may represent only a fraction of DNA damage induced by tobacco smoke. Aromatic amines are another family of compounds found in ETS that can form adducts with DNA (Talaska et al. 1991a
; Hecht 2001
). Fourth, there may have been sources of PACs other than ETS—such as exhaust from automobiles or dietary intake—that were not measured by the air nicotine dosimeters. Exposure to automobile exhaust and consumption of charbroiled foods have both been linked to higher PAC-DNA adduct levels (Rothman et al. 1993
; Perera et al. 2005
). Lastly, all of the subjects in this study had asthma. It is unknown whether these results are generalizable to children without asthma.
Despite the results, our study did employ some unique strategies. We assembled a bi-racial cohort of tobacco-exposed children with asthma, which allowed us to explore factors that might contribute to DNA damage. While other studies have used ELISA tests, we used 32
P-postlabeling with nuclease P1 enhancement to measure DNA adducts in our study sample. This process allowed for the detection of very low levels of PAC-DNA adducts (0.01 adducts per 109
nucleotides) without prior knowledge of the identity of the compounds (Reddy et al. 1981
; Reddy and Randerath 1986
). We assessed ETS exposure in the home using a validated air nicotine dosimeter. The dosimeters provided an objective measurement of the child’s in-home exposure to ETS for 6 months prior to the measurement of the DNA adducts. To our knowledge, this is the first
study to attempt to correlate air nicotine levels with DNA adducts in a cohort of ETS-exposed children with asthma. Also, we demonstrated a non-significant trend toward an inverse relationship between air cleaner use and DNA adduct levels. Even though there were no differences in adduct levels between subjects with active and control filters, it is notable that increased use of the air cleaner trended toward lower DNA adduct levels. Potentially, improved room ventilation may reduce DNA adduct levels. Further studies are required to confirm and extend these findings.