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首页> 美国卫生研究院文献>other >Mutagenicity Stable DNA Adducts and Abasic Sites Induced in Salmonella by Phenanthro34-b- and Phenanthro43-bthiophenes Sulfur Analogs of Benzocphenanthrene
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Mutagenicity Stable DNA Adducts and Abasic Sites Induced in Salmonella by Phenanthro34-b- and Phenanthro43-bthiophenes Sulfur Analogs of Benzocphenanthrene

机译：苯并c菲的硫代类似物菲34-b-和菲43-b噻吩在沙门氏菌中诱变稳定的DNA加合物和无碱基位点。

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Sulfur-containing polycyclic aromatic hydrocarbons (thia-PAHs or thiaarenes) are common constituents of air pollution and cigarette smoke, but only a few have been studied for health effects. We evaluated the mutagenicity in Salmonella TA98, TA100, and TA104 of two sulfur-containing derivatives of benzo[c]phenanthrene, phenanthro[3,4-b]thiophene (P[3,4-b]T), and phenanthro[4,3-b]thiophene (P[4,3-b]T) as well as their dihydrodiol and sulfone derivatives. In addition, we assessed levels of stable DNA adducts (by 32P-postlabeling) as well as abasic sites (by an aldehydic-site assay) produced by six of these compounds in TA100. P[3,4-b]T and its 6,7- and 8,9-diols, P[3,4-b]T sulfone, P[4,3-b]T, and its 8,9-diol were mutagenic in TA100. P[3,4-b]T sulfone, the most potent mutagen, was approximately twice as potent as benzo[a]pyrene in both TA98 and TA100. Benzo-ring dihydrodiols were much more potent than K-region dihydrodiols, which had little or no mutagenic activity in any strain. P[3,4-b]T sulfone produced abasic sites and not stable DNA adducts; the other five compounds examined, B[c]P, B[c]P 3,4-diol, P[3,4-b]T, P[3,4-b]T 8,9-diol, and P[4,3-b]T 8,9-diol, produced only stable DNA adducts. P[3,4-b]T sulfone was the only compound that produced significant levels of frameshift mutagenicity and induced mutations primarily at GC sites. In contrast, B[c]P, its 3,4-diol, and the 8,9 diols of the phenanthrothiophenes induced mutations primarily at AT sites. P[3,4-b]T was not mutagenic in TA104, whereas P[3,4-b]T sulfone was. The two isomeric forms (P[3,4-b]T and P[4,3-b]T) are apparently activated differently, with the latter, but not the former, involving a diol pathway. This study is the first illustrating the potential importance of abasic sites in the mutagenicity of thia-PAHs.
机译：含硫的多环芳烃（thia-PAHs或thiaarenes）是空气污染和香烟烟雾的常见成分，但对健康影响的研究很少。我们评估了沙门氏菌TA98，TA100和TA104中两种苯并[c]菲，菲[3,4-b]噻吩（P [3,4-b] T）和菲[4]的含硫衍生物的致突变性。 ，3-b]噻吩（P [4,3-b] T）及其二氢二醇和砜衍生物。此外，我们评估了TA100中六个这样的化合物产生的稳定DNA加合物（通过 32 P后标记）的水平以及无碱基位点（通过醛位分析）。 P [3,4-b] T及其6,7-和8,9-二醇，P [3,4-b] T砜，P [4,3-b] T及其8,9-二醇在TA100中具有致突变性。最有效的诱变剂P [3,4-b] T砜在TA98和TA100中的效力约为苯并[a] re的两倍。苯环二氢二醇比K区二氢二醇强得多，后者在任何菌株中几乎没有诱变活性。 P [3,4-b] T砜产生无碱基位点，而不是稳定的DNA加合物；检查了其他五个化合物，B [c] P，B [c] P 3,4-二醇，P [3,4-b] T，P [3,4-b] T 8,9-二醇和P [4,3- b ] T 8,9-二醇仅产生稳定的DNA加合物。 P [3,4- b ] T砜是唯一会产生大量移码致突变性并主要在GC位点引起突变的化合物。相反，苯并噻吩的B [ c ] P，其3,4-二醇和8,9二醇主要在AT位点诱导突变。在TA104中，P [3,4- b ] T不致突变，而P [3,4- b ] T砜具有致突变性。两种同分异构形式（P [3,4- b ] T和P [4,3- b ] T）显然被不同地激活，但后者前者涉及二醇途径。这项研究首次说明了无碱基位点在thia-PAHs致突变性中的潜在重要性。

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