• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6591-6593
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• 2013

Background: Environmental tobacco smoking (ETS) significantly contributes to morbidity and mortality and is a known risk factor for lung cancer development in lifelong nonsmokers. The metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs) have now emerged as leading biomarkers for the study of carcinogen exposure in non-smokers exposed to ETS. Materials and Methods: We carried out our study on NNAL in the urine of non-smokers exposed to ETS and the association between ETS and lung cancer. Subjects were enrolled from 2008-2010. NNAL was analyzed for 74 non-smoking lung cancer and 85 healthy controls. The main objective of this study was to provide an estimate of the risk of lung cancer from exposure to ETS in the Korean population. Results: The mean NNAL concentration in urine was significantly lower in non-smoking patient groups (n=74) than in control groups (n=85) ($4.7{\pm}15.0$ pg/mg, $6.5{\pm}17.9$ pg/mg, respectively, Mann-Whitney U test, p<0.001). Conclusions: The urine NNAL of non-smoking patients with lung cancer was not elevated with regard to the non-smoking control group. This may be due to life-style changes after diagnosis. A prospective study will be needed to evaluate the association of NNAL and non-smoking lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5311-5317
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• 2015

Cigarette smoke derivatives like NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol) are well-known carcinogens. We analyzed the interaction of enzymes involved in the NER (nucleotide excision repair) pathway with ligands (NNK and NNAL). Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. The highest obtained docking energy between NNK and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.13 kcal/mol, -7.27 kcal/mol, -8.05 kcal/mol and -7.58 kcal/mol respectively. Similarly the highest obtained docking energy between NNAL and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.46 kcal/mol, -7.94 kcal/mol, -7.83 kcal/mol and -7.67 kcal/mol respectively. In order to find out the effect of NNK and NNAL on enzymes involved in the NER pathway applying protein-protein interaction and protein-complex (i.e. enzymes docked with NNK/NNAL) interaction analysis. It was found that carcinogens are well capable to reduce the normal functioning of genes like RAD23A (HR23A), CCNH, CDK7 and CETN2. In silico analysis indicated loss of functions of these genes and their corresponding enzymes, which possibly might be a cause for alteration of DNA repair pathways leading to damage buildup and finally contributing to cancer formation.

• 생명과학회지
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• 제20권5호
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• pp.703-709
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• 2010

Glucuronidation은 NNAL [4-(methylnitrosamno)-1-(3-pyridyl)-1-butanol]의 주요 pathway이며, UGT2B의 family인 UGT2B17 (UGT, uridine diphospho-glucuronosyltransferase) 유전자는 발암원의 glucuronidation에 관여 한다. UGT2B17 결손은 NNAL의 감소 수준과 특정 암에 있어 위험도를 증가시킨다. UGT2B17 유전자의 copy 수는 사람에서 개인별로 0~2로 다양하다. 본 연구에서는 UGT2B17 결손이 폐암의 위험도와 연관성을 가지는 가를 알아보기 위해 한국인인 271명의 대조군과 176명의 폐암환자의 샘플로 PCR 방법으로 CNV를 조사하였다. 그 결과, 현재까지 보고된 백인과 흑인에 비해 한국인에서 결실 대립형질이 현저히 높게 나타났다. 백인에서 유전자 두 개 모두가 결실된 0 copy 수가 약 10%를 나타낸 것에 비해, 본 연구의 한국인에서는 0 copy 수가 약 74%를 나타내었다. 더욱이 양 쪽 결실이 여성그룹에서 전반적으로 남성그룹에 비해 높게 나타났다. 그러나 UGT2B17 유전자가 CNV와 폐암과의 연관성은 찾을 수 없었다. 이러한 결과는 UGT2B17 유전자의 결실이 폐암의 감수성과는 연관되어 있지 않으나, UGT2B17 CNV 다형성이 인종간의 진화적 분석의 유용한 마커로 사용이 가능할 것으로 사료된다.

• 한국연초학회지
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• 제31권1호
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• pp.58-67
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• 2009

Biomarkers could be critical and useful tools for assessing the biological effects of smoking and detecting differences between potentially reduced exposure product (PREP) and conventional cigarettes. Smoking-related biomarkers can be classified into three categories as biomarkers of exposure, biomarkers of effects, and biomarkers of potential harm. When compared with the biomarkers of effects or harm, the biomarkers of exposure for chemical constituents of cigarette smoke are well established and characterized. In addition, they could offer the important information in understanding how cigarette smoke interacts with biological molecules and causes the disease to human. Therefore, we provide an overview of 6 biomarkers of exposure (Nicotine and nicotine metabolites, Carboxyhaemoglobin, NNAL (4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol) and NNAL - glucuronide, 3-Hydroxypropyl-mercapturic acid, and Monohydroxy-butenyl-mercapturic acids, and Urine mutagenicity) which were validated through extensive research and clinical experience. These reliable biomarkers could help identify the efficacy of PREP by predicting early toxicological effects and lead to improve it.