Mutagenesis induced by benzo[a]pyrene in lacZ mouse mammary and oral tissues: comparisons with mutagenesis in other organs and relationships to previous carcinogenicity assays.
Mutagenesis induced by benzo[a]pyrene in lacZ mouse mammary and oral tissues: comparisons with mutagenesis in other organs and relationships to previous carcinogenicity assays.
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lacZ 小鼠乳腺和口腔组织中苯并[a]芘诱导的诱变：与其他器官诱变的比较以及与先前致癌性测定的关系。
DOI：
10.1093/carcin/20.6.1103
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发表时间：
1999
期刊：
影响因子：
4.7
通讯作者：
Guttenplan,JB
中科院分区：
文献类型：
--
作者：
Kosinska,W;vonPressentin,MD;Guttenplan,JB
到目前为止，在体内致突变试验已检测到苯并[a]芘（B[a]P）在许多器官中的器官特异性效应，但在口腔组织和乳腺中未检测到。先前的研究表明，小鼠舌头是B[a]P掺入饲料时诱导肿瘤发生的靶点，多环芳烃是小鼠乳腺组织中的致癌物。为了评价lacZ小鼠血清活诱变试验检测这些靶组织中突变的能力，我们测量了B[a]P在乳腺和口腔组织中诱导的诱变。口腔组织由舌头或来自口腔中几个部位的口腔组织的混合物组成。当以相对高剂量灌胃给药时，B[a]P在乳腺组织中的致突变性高于大多数其他受试器官（肝、肺和肾），在低剂量下，致突变性高于肝，但不高于肺。当在饮用水乳剂中给药时，B[a]P在口腔组织中的致突变性高于肝脏，而在肺中的致突变性略低。无论剂量如何，结肠中的致突变活性最大，远高于其他器官。在这里观察到的诱变和以前研究中的致癌作用之间观察到合理的相关性，尽管注意到一些差异。据我们所知，这是首次报道非肿瘤乳腺和口腔组织中的体内突变，结果表明这些器官可以有效地将B[a]P代谢为遗传毒性产物，尽管不能排除来自肝脏的活性代谢物的一些转运。ThelacZ小鼠致突变试验可能是一种较短期的替代致癌试验，用于研究影响乳腺和口腔组织致癌起始的因素。然而，它对实际肿瘤形成的预测性较低。
Thus far,in vivomutagenic assays have detected organ-specific effects of benzo[a]pyrene (B[a]P) in a number of organs, but not in oral tissues and breast. Previous studies have shown that the mouse tongue is a target for tumorigenesis induced by B[a]P when incorporated into feed, and polycyclic aromatic hydrocarbons are carcinogens in mouse mammary tissue. In order to evaluate the capacity of thelacZmousein vivomutagenesis assay to detect mutations in these target tissues, we have measured mutagenesis induced by B[a]P in breast and oral tissues. The oral tissue consisted of either tongue or a mixture of oral tissues from several sites in the oral cavity. B[a]P was more mutagenic in breast tissue than in most other organs tested (liver, lung and kidney) when administered at relatively high dose by gavage, and more mutagenic than in liver, but not lung, at low dose. When administered in an emulsion in drinking water, B[a]P was more mutagenic in oral tissues than in liver, and somewhat less mutagenic than in lung. Regardless of dose, the mutagenic activity was greatest in colon where it was much higher than in other organs. A reasonable correlation was observed between mutagenesis observed here and carcinogenesis in previous studies although some differences were noted. To our knowledge, this represents the first report ofin vivomutagenesis in non-tumor mammary and oral tissue, and the results indicate these organs can efficiently metabolize B[a]P to genotoxic products, although some transport of active metabolites from the liver cannot be ruled out. ThelacZmouse mutagenesis assay may represent a shorter term alternative to carcinogenesis assays for investigations of factors affecting initiation of carcinogenesis in mammary and oral tissues. However, it is less predictive of actual tumor formation.