산모 흡연 연구과제

15
임임 임임 임임임임 임임 임임 임임 임임임임임임임 임임임

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임신 초기 임신부의 흡연 노출 평가

진단검사의학과 곽호석

Smoking patterns during preg-nancy

평균 4 주

평균 7 주

Quantitation of Metabolites of NNK af-ter Cessation of Smokeless Tobacco Use

Time post-cessation (days)

Smoking

NNAL t1/2: 10-18 days > cotinine t1/2 : 1days

0 2 4 6 8 10

12

14

16

18

20

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

120.0%

CotinineNNAL

DayC

ocncentr

ati

on (

%)

The metabolic activation and inactivation of NNK

* 11β-HSD: 11β-hydroxysteroid dehydrogenase

Steroid hormonesDrug: diureticsDrug: block 11β-HSDDrugDrug: flavonoidFlavanone

Similar structure: hormones

Total NNAL after exposure to sidestream smoke (4hr)

Urine Concentrations of a Tobacco-Specific Ni-trosamine Carcinogen in the U.S. Population

from Secondhand Smoke Exposure

NNAL concentration according to cigarette brand

미국 벡터 (Vector) 사는 지난 2001 년 발암성 물질을 줄인 담배 ‘ OMNI’ 를 선보인 데 이어 , 2003 년에는 저니코틴 담배 ‘ QUEST’ 를 출시했다 . 이 담배는 기존 담배와 비교해 니코틴 함량을 97% 낮춘 GM( 유전자조작 ) 담배로 제조됐다 . 그러나 향과 맛 등의 주요 특징들은 기존 담배와 거의 동일한 것으로 전해졌다 .

A Vector Tobacco website claimed Omni produced a 53% reduction in exposure to NNK.

NNAL 분석

Comparison of analytical method

Author Urine vol. LOQ (pg/mL)

Analytical concen-tration of LOQ

Sample prepara-tion

Hou Hongwei et al. (2012) 5 mL 0.99 50 pg/mL

Enzyme reaction(overnight), MIP

Showket H. Bhat et al. (2011) 0.25 mL 20 50 pg/mL

Enzyme reaction(20h), derivatization(12h), SPE

Dominique Kavvadias et al. (2009) 6 mL 5 300 pg/mL

Enzyme reaction(14h), MIP, SPE

Yang Xia et al. (2005) 5 mL 1.7 425 pg/mL

Enzyme reaction(24h), MIP

Sample preparation

• Enzyme reaction: beta-glucuronidase (overnight)

• NNAL extraction: MIP(molecular imprinting polymer) column (2hr)

• Measurement of NNAL: LC-MS/MS (6min/sample)

Chromatograms of the ion transition for NNAL and its deuterated internal standard in urine sample of a

smoker

5 ng/mL 500 ng/mL

NNAL-d3 NNAL-d3

NNAL NNAL

Urine: 1mL (20cigarette/day, male)Non-enzyme digestion, MIP column

Microwave-Assisted Enzyme-Cat-alyzed Reactions

Metabolism of TSAN

NNA has been described as a very reactive aldehyde which has never been quantified in tobacco or tobacco smoke. There has been considerable interest in recent yearsin the chemical composition of smokeless tobacco products based around health concerns associatedwith their use

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