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人造煤气厂残渣中的多环芳烃成分与小鼠肺和前胃DNA的共价结合。

Covalent binding of polycyclic aromatic hydrocarbon components of manufactured gas plant residue to mouse lung and forestomach DNA.

作者信息

Weyand E H, Wu Y

机构信息

College of Pharmacy, Department of Pharmaceutical Chemistry, Rutgers, State University of New Jersey, Piscataway 08855-0789, USA.

出版信息

Chem Res Toxicol. 1995 Oct-Nov;8(7):955-62. doi: 10.1021/tx00049a009.

Abstract

The present study characterized the DNA adducts induced by manufactured gas plant residue (MGP) and benzo[alpha]pyrene (B[alpha]P) in mouse lung and forestomach. The dose levels used in the present study were comparable to the levels used in a previous animal bioassay. Adduct formation was evaluated in female A/J mice (7 weeks old) fed MGP (0.25%) or B[alpha]P (16 and 98 ppm) for 14 days. In addition, adduct formation was also evaluated in mice 24 h after the ip administration of 1.8 mg of B[alpha]P in 0.5 mL of tricaprylin. 32P-Postlabeling combined with multidimensional TLC and reverse phase HPLC was used to evaluate hydrocarbon-DNA adducts. HPLC separation of chemical-DNA adducts formed in lung following MGP ingestion resulted in three distinct peaks of radioactivity eluting at 22, 32.4, and 33.5 min. These peaks accounted for 13, 10, and 41% of the total adducts detected. The adducts isolated from forestomach eluted as a series of minor peaks with two more distinct peaks of radioactivity at 32.4 and 33.5 min. These peaks accounted for 47 and 32% of the total adducts detected in forestomach, respectively. Ingestion of B[alpha]P (16 or 98 ppm) and the ip administration of B[alpha]P resulted in a single major adduct with a retention time of 32.4 min. The DNA adducts formed from MGP administration were further characterized by comparison with adducts formed following the administration of individual hydrocarbons and a mixture of hydrocarbons.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

本研究对人造煤气厂残渣(MGP)和苯并[a]芘(B[a]P)在小鼠肺部和前胃中诱导产生的DNA加合物进行了表征。本研究中使用的剂量水平与先前动物生物测定中使用的水平相当。对7周龄雌性A/J小鼠喂食MGP(0.25%)或B[a]P(16和98 ppm)14天,评估加合物的形成。此外,还对腹腔注射0.5 mL三辛酸甘油酯中1.8 mg B[a]P的小鼠在24小时后评估加合物的形成。采用32P后标记结合多维薄层色谱和反相高效液相色谱法评估烃-DNA加合物。摄入MGP后在肺部形成的化学-DNA加合物经高效液相色谱分离,产生三个不同的放射性峰,分别在22、32.4和33.5分钟洗脱。这些峰分别占检测到的总加合物的13%、10%和41%。从前胃分离的加合物洗脱为一系列小峰,在32.4和33.5分钟有两个更明显的放射性峰。这些峰分别占在前胃中检测到的总加合物的47%和32%。摄入B[a]P(16或98 ppm)以及腹腔注射B[a]P导致出现一个保留时间为32.4分钟的单一主要加合物。通过与单独施用碳氢化合物和碳氢化合物混合物后形成的加合物进行比较,进一步表征了施用MGP形成的DNA加合物。(摘要截短于250字)

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