The results of this study provide a plausible lead for understanding epidemiologic studies that show a higher risk of lung cancer in nonsmoking women who regularly cook with high temperature oils (3
). Significantly higher levels of mercapturic acid biomarkers of the volatile organic carcinogens and toxicants acrolein, crotonaldehyde, and benzene were observed in the women who cooked compared to controls. These results provide an initial biochemical link between previous studies demonstrating the presence of these compounds in cooking oil fumes (12
) and the epidemiologic studies of lung cancer. Many other volatile organic compounds, some of which may have toxic properties, have been detected in cooking oil fumes (13
), and our results suggest that uptake of these volatiles might also be increased during wok cooking, although biomarkers for most of them are not available.
Our finding of elevated levels of SPMA, a biomarker of benzene uptake, in the urine of women who cooked is particularly interesting. Levels of this biomarker were approximately 3 times greater in the women who cooked than in controls. Benzene is considered carcinogenic to humans by the U.S. Dept. of Health and Human Services and by the International Agency for Research on Cancer (32
). The most common finding in epidemiologic studies of benzene exposure is increased risk for leukemia, and benzene is considered a known human leukemogen. However, one large study of industrial exposure carried out in China demonstrated an increased risk for lung cancer in those exposed to benzene (34
). Benzene is a multipotent carcinogen in laboratory animals, inducing a variety of types of tumors, including lung tumors (32
We also found elevated levels of HPMA and HBMA, biomarkers of uptake of acrolein and its homologue crotonaldehyde, respectively. Both acrolein and crotonaldehyde are weak carcinogens, and neither is known to target the lung (22
). However, acrolein is cilia-toxic and thus may impede the clearance of toxicants and other foreign substances from the lung (36
). Acrolein is highly reactive with proteins and may be involved in inflammation (37
). Both acrolein and crotonaldehyde are products of oxidative damage and both are known to react with DNA, producing adducts, some of which have miscoding properties (39
). These adducts have been detected in various in vitro systems and in the human lung (41
). There is a background level of acrolein and crotonaldehyde-DNA adducts in humans, which may be related to oxidative damage and lipid peroxidation (41
). Our results suggest that such damage may be exacerbated by exposure to fumes from wok cooking, and this should be examined in future studies. Acrolein-DNA adducts have also been associated with mutations in the p53
tumor suppressor gene, as seen in lung cancer (45
). Collectively, these results suggest that the increased exposure to acrolein and crotonaldehyde observed here may play some role in lung cancer induction associated with wok cooking.
The increases in levels of mercapturic acids of benzene, acrolein, and crotonaldehyde observed in this study were not nearly as great as seen in smokers (25
). In a recent study, we found that levels of these mercapturic acids decreased by 7–8 fold three days after smokers stopped smoking to levels that were generally consistent with those observed in the non-smoking women in our study (25
). Cigarette smoking provides a far greater exposure to these compounds than does wok cooking, so the smaller increases seen in this study are fully plausible (14
). The high biomarker levels seen in smokers is consistent with the known amounts of benzene, acrolein, and crotonaldehyde in cigarette smoke, and with the far higher risk for lung cancer from smoking compared to indoor fume exposure.
We did not observe increases in biomarkers of exposure to 1,3-butadiene or PAH. Levels of 1,3-butadiene in fumes from heated oils are far lower than those of a number of other volatile compounds such as acrolein (14
). Therefore, this result is not unexpected. While PAH have been identified in cooking oil fumes(12
), they are high molecular weight, non-volatile compounds. Thus, their uptake under normal cooking circumstances would be less likely than that of the more volatile compounds such as benzene, acrolein, and crotonaldehyde
-ethylidene-dG is a biomarker of acetaldehyde exposure which is moderately increased by both cigarette smoking and alcohol consumption (29
). However, all subjects analyzed to date have appreciable levels of this biomarker, even if they do not smoke or drink, because there are multiple sources of acetaldehyde exposure. The average levels of N2
-ethylidene-dG observed here were considerably higher than in our previous studies (29
), which may have diminished our ability to detect a change in this biomarker due to exposure to acetaldehyde, a known constituent of cooking fumes. The basis for the high DNA adduct levels observed here requires further investigation. One possibility is exposure from vegetation fires in Indonesia, which may release volatiles which were carried to Singapore by prevailing winds.
One curious finding was the lower level of HEMA, a biomarker of ethylene oxide exposure, in the women who cooked than in controls. Ethylene oxide has been identified as a constituent of cooking fumes (15
). However, it could also be formed endogenously by oxidation of ethylene (47
). The endogenous formation of ethylene oxide could lead to considerable variation in HEMA levels in a relatively small study such as ours. Further studies are required to investigate this finding.
One previous study carried out in Chinese restaurant workers examined the effects on biomarkers of exposure to cooking oil fumes (16
). Pan et al found that urinary levels of 1-HOP and 8-hydroxy-dG, a biomarker of oxidative damage, were significantly higher in kitchen staff than in service staff. They concluded that oxidative DNA damage was associated with exposure of Chinese restaurant workers to cooking oil fumes and also observed that the response was greater in female than in male restaurant workers.
There are some limitations to this study. First, the size was quite small, with only 42–54 exposed subjects and 50 general population controls. Second, we do not have information on the cooking habits of the general population controls. Third, we do not know the exact half-lives of the biomarkers studied. Therefore a spot urine collected at randomly timed points would not be optimal for the assessment of biomarkers with short half-lives. In spite of these limitations, we observed significant differences in three carcinogen and toxicant biomarkers, which supports the hypothesis that exposure to cooking fumes is a cause of lung cancer in Chinese women.
In summary, the results of this study demonstrate elevated levels of volatile organic compound biomarkers in Chinese women who regularly cook at home. These biomarkers reflect increased exposure to volatile carcinogens and toxicants such as benzene, acrolein, and crotonaldehyde. While larger studies are needed to confirm these results, the present data, together with multiple epidemiologic studies, demonstrate the urgent need for preventive measures such as improved ventilation to efficiently remove cooking oil fumes.