2-butenal and Lung-Neoplasms

Crotonaldehyde (CA), a prominent component of cigarette smoke (CS) is a pervasive environmental pollutant that is a highly toxic, unsaturated aldehyde. Exposure to CA-rich pollutants has been linked to the emergence of many malignancies in humans. To better understand the role of CA in biomolecule modification, this study investigated the detailed structural alterations in low-density lipoprotein (LDL) modified by CA, as well as the immunogenicity of the modified protein in experimental animals and the search for autoantibodies in various cancers patients.In vitro, results indicated alterations in secondary and tertiary structures; examined using UV-visible, fluorescence, far-UV circular dichroism, and Fourier transform infrared spectroscopy techniques. Changes in the oxidation status of LDL were studied by carbonyl content assay and NBT assay. ThT binding assay, scanning, and transmission electron microscopy were used to study aggregate formation. The findings revealed significant structural damage in LDL modified by CA. The modification resulted in the unmasking of hydrophobic clusters, the loss of the protein α-helix, and the formation of β-pleated sheet structure. The amyloid aggregate formation was confirmed through ThT microscopy and electron spectroscopy. Rabbits immunized with crotonaldehyde; lead to structural changes in the LDL; that acted as extra antigenic determinants, eliciting strong antibody response. Immunoglobulin response is highly specific for modified LDL as demonstrated by the ELISA. The presence of antibodies against CA-modified LDL was confirmed by the immunoglobulin content of blood sera from human subjects with lung cancer, and competitive ELISA demonstrated the specificity of these antibodies. This study offers insights into the CA-mediated LDL modification and immunogenicity in lung cancer that will have diagnostic importance.

Topics: Aldehydes; Animals; Autoantibodies; Humans; Lipoproteins, LDL; Lung Neoplasms; Rabbits

Lung cancer is unusually common among non-smoking women in Southeastern Asia but the causes of this frequently fatal disease are not well understood. Several epidemiology studies indicate that inhalation of fumes from high temperature Chinese style cooking with a wok may be a cause. Only one previous study investigated uptake of potential toxicants and carcinogens by women who cook with a wok. We enrolled three-hundred twenty-eight non-smoking women from Singapore for this study. Each provided a spot urine sample and answered a questionnaire concerning their cooking habits and other factors. The urine samples were analyzed by liquid chromatography-tandem mass spectrometry for mercapturic acid metabolites of acrolein (3-hydroxypropylmercapturic acid), crotonaldehyde (3-hydroxy-1-methylpropylmercapturic acid), and benzene (S-phenylmercapturic acid), accepted biomarkers of uptake of these toxic and carcinogenic compounds. We observed statistically significant effects of wok cooking frequency on levels of 3-hydroxypropylmercapturic acid and 3-hydroxy-1-methylpropylmercapturic acid, but not S-phenylmercapturic acid. Women who cooked greater than 7 times per week had a geometric mean of 2600 (95% CI, 2189-3090) pmol/mg creatinine 3-hydroxypropylmercapturic acid compared to 1901 (95% CI, 1510-2395) pmol/mg creatinine when cooking less than once per week (P for trend 0.018). The corresponding values for 3-hydroxy-1-methylpropylmercapturic acid were 1167 (95% CI, 1022-1332) and 894 (95% CI, 749-1067) pmol/mg creatinine (P for trend 0.008). We conclude that frequent wok cooking leads to elevated exposure to the toxicants acrolein and crotonaldehyde, but not benzene. Kitchens should be properly ventilated to decrease exposure to potentially toxic and carcinogenic fumes produced during Chinese style wok cooking.

Topics: Acetylcysteine; Acrolein; Aged; Aldehydes; Asian People; Benzene; Biomarkers; Carcinogens; Cooking; Female; Humans; Lung Neoplasms; Middle Aged; Singapore; Smoking

The Multiethnic Cohort epidemiology study has clearly demonstrated that, compared to Whites and for the same number of cigarettes smoked, African Americans and Native Hawaiians have a higher risk for lung cancer whereas Latinos and Japanese Americans have a lower risk. Acrolein and crotonaldehyde are two important constituents of cigarette smoke which have well documented toxic effects and could play a role in lung cancer etiology. Their urinary metabolites 3-hydroxypropylmercapturic acid (3-HPMA) and 3-hydroxy-1-methylpropylmercapturic acid (HMPMA), respectively, are validated biomarkers of acrolein and crotonaldehyde exposure. We quantified levels of 3-HPMA and HMPMA in the urine of more than 2200 smokers from these five ethnic groups, and also carried out a genome wide association study using blood samples from these subjects. After adjusting for age, sex, creatinine, and total nicotine equivalents, geometric mean levels of 3-HPMA and HMPMA were significantly different in the five groups (P < 0.0001). Native Hawaiians had the highest and Latinos the lowest geometric mean levels of both 3-HPMA and HMPMA. Levels of 3-HPMA and HMPMA were 3787 and 2759 pmol/ml urine, respectively, in Native Hawaiians and 1720 and 2210 pmol/ml urine in Latinos. These results suggest that acrolein and crotonaldehyde may be involved in lung cancer etiology, and that their divergent levels may partially explain the differing risks of Native Hawaiian and Latino smokers. No strong signals were associated with 3-HPMA in the genome wide association study, suggesting that formation of the glutathione conjugate of acrolein is mainly non-enzymatic, while the top significant association with HMPMA was located on chromosome 12 near the TBX3 gene, but its relationship to HMPMA excretion is not clear.

Topics: Acetylcysteine; Acrolein; Aged; Aldehydes; Ethnicity; Female; Hawaii; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking