Metabolism of [D10]phenanthrene to tetraols in smokers for potential lung cancer susceptibility assessment: comparison of oral and inhalation routes of administration.
نویسندگان
چکیده
Polycyclic aromatic hydrocarbons (PAHs) are believed to be among the causative agents for lung cancer in smokers. PAHs require metabolic activation for carcinogenicity. One pathway produces diol epoxides that react with DNA, causing mutations. Because diol epoxides are converted to tetraols, quantitation of tetraols can potentially be used to identify smokers who may be at higher risk for lung cancer. Our approach uses [D(10)]phenanthrene, a labeled version of phenanthrene, a noncarcinogenic PAH structurally analogous to carcinogenic PAH. Although smokers are exposed to PAH by inhalation, oral dosing would be more practical for phenotyping studies. Therefore, we investigated [D(10)]phenanthrene metabolism in smokers after administration by inhalation in cigarette smoke or orally. Sixteen smokers received 10 μg of [D(10)]phenanthrene in a cigarette or orally. Plasma and urine samples were analyzed for [D(10)]r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene ([D(10)]PheT), the major end product of the diol epoxide pathway, by gas chromatography-negative ion chemical ionization-tandem mass spectrometry. The ratios of [D(10)]PheT (oral dosing/inhalation) in 15 smokers were 1.03 ± 0.32 and 1.02 ± 0.35, based on plasma area under the concentration-time curve (0-∞) and total 48-h urinary excretion, respectively. Overall, there was no significant difference in the extent of [D(10)]PheT formation after the two different routes of exposure in smokers. A large interindividual variation in [D(10)]PheT formation was observed. These results demonstrate that the level of [D(10)]PheT in urine after oral dosing of [D(10)]phenanthrene can be used to assess individual capacity of PAH metabolism by the diol epoxide pathway.
منابع مشابه
Evaluation of the risk of lung cancer associated with NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism in male current cigarette smokers from the Eastern India
NAD(P)H: quinone oxidoreductase 1 (NQO1) is an endogenous cellular defence mechanism against several carcinogenic quinones derived from cigarette smoke. NQO1 C609T polymorphism is a strong determinant of NQO1 structure and function. The people with mutant allele for this polymorphism has significantly reduced NQO1 activity. In this study, we tried to evaluate the risk of lung cancer as...
متن کاملPharmacokinetics and Biodistribution of Rhopalurus junceus Scorpion Venom in Tumor-Bearing Mice after Intravenous and Oral Administration
Introduction: Rhopalurus junceus scorpion venom has shown potential for anticancer treatment. However, there are no scientific evidence about venom pharmacokinetic (PK) and biodistribution (BD) in tumor-bearing mice. Methods: 131I-labeled venom was administrated by intravenous (IV) and oral (PO) routes at the single dose of 12.5 mg/kg. Mice were sacrificed and blood samples, major organs, and t...
متن کاملThe Assessment of Serum Apelin-12 Level in a Variety of Pulmonary Malignancies in Smokers
Background: Apelin has recently been considered as an adipokine secreted from visceral fat. Apelin and itsreceptor exist in many tissues including lung and play significant roles in many physiological andpathological activities. However, serum level of apelin-12 is unknown in smokers and in various types of lungmalignancies. There...
متن کاملNo needle to fear: An approach to needle phobic patients
18F-FDG is the most commonly used radioisotope in PET scanning and is administered intravenously. When patients cannot cannulated, there are limited options available for functional tumour assessment. A fifty year old male presented for investigation of a suspected lung carcinoma identified during investigation of pneumonia. The patient had a severe needle phobia, intellectual dis...
متن کاملDietary Iron Source and Lung Cancer Risk: A Case-Control Study in Uruguayan Men
Introduction: Iron metabolism was found to be implicated in several cancers. Few epidemiologic studies; focusing on iron intake and lung cancer (LC), reported positive associations between heme iron and red meat. Based on estimates of iron contents in representative foods, we conducted the present study with the aim of analyzing dietary iron and its role on the incidence of LC in Uruguayan men,...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 338 1 شماره
صفحات -
تاریخ انتشار 2011