Mersch-Sundermann V, Emig M, Reinhardt A, Helbich H M
Institut für Medizinische Mikrobiologie und Hygiene, Ruprecht-Karls-Universität Heidelberg.
Gesundheitswesen. 1996 Jul;58(7):400-5.
In the present study a mixture containing the 11 PCB major components identified in fatty tissues of children was examined for its potency to enhance the toxification of pregenotoxicants (cogenotoxicity) in the liver. As a basis for the study GC/MS PCB analyses of 207 fatty tissue samples of children were used. The PCB mixture was produced on this basis. As a model for the identification of the cogenotoxic potency of the PCB mixtures an in vivo/in vitro enzyme induction assay was developed. The goal of the study was to clarify the question, whether the in vivo pretreatment of rats with a complex PCB pattern derived from children led to a synergism of cogenotoxicants and pregenotoxicants with regard to the enhancement of the in vitro toxification of benzo[a]pyrene (B[a]P) and 2-aminoanthracene (2-AA) to DNA reactive metabolites. Using the SOS-Chromotest as the in vitro part of the induction assay, all liver enzyme fractions of PCB pretreated rats (S9PCB) showed an increase of the toxification of the pregenotoxicants B[a]P and 2-AA in comparison to enzyme factions of untreated animals (S9(0)). With regard to the reactivity pattern it may be supposed that the PCB mixture probably induced cytochrome P450-dependent oxigenases of the subclasses CYP1A1 and CYP1A2. Additionally, it seems to be of interest that the use of S9(0) fractions did not lead to any or only to weak toxification of B[a]P and 2-AA. Thus, a synergism of cogenotoxicants and pregenotoxicants could be confirmed. PCB could be identified in fatty tissues of children in amounts up to 1 mg/kg. Additionally, pregenotoxicants like polycyclic aromates, mycotoxins and/or aminocontaining compounds, are available in almost all environmental sources. Therefore, from the present point of view, a genetic risk caused by PCB in humans (children) cannot be excluded.
在本研究中，检测了一种含有在儿童脂肪组织中鉴定出的11种多氯联苯主要成分的混合物，以评估其增强肝脏中前遗传毒性物质（共遗传毒性）毒性的能力。作为该研究的基础，使用了对207份儿童脂肪组织样本进行的气相色谱/质谱多氯联苯分析。在此基础上制备了多氯联苯混合物。作为鉴定多氯联苯混合物共遗传毒性能力的模型，开发了一种体内/体外酶诱导试验。该研究的目的是明确这样一个问题，即给大鼠进行源自儿童的复杂多氯联苯模式的体内预处理，是否会导致共遗传毒性物质和前遗传毒性物质在增强苯并[a]芘（B[a]P）和2-氨基蒽（2-AA）向DNA反应性代谢物的体外毒性方面产生协同作用。使用SOS-显色试验作为诱导试验的体外部分，与未处理动物的酶组分（S9(0)）相比，多氯联苯预处理大鼠的所有肝脏酶组分（S9PCB）均显示前遗传毒性物质B[a]P和2-AA的毒性增加。关于反应模式，可以推测多氯联苯混合物可能诱导了细胞色素P450依赖性氧化酶的CYP1A1和CYP1A2亚类。此外，似乎值得关注的是，使用S9(0)组分不会导致B[a]P和2-AA产生任何毒性或仅产生微弱毒性。因此，可以确认共遗传毒性物质和前遗传毒性物质之间存在协同作用。在儿童脂肪组织中可检测到含量高达1 mg/kg的多氯联苯。此外，几乎在所有环境来源中都存在前遗传毒性物质，如多环芳烃、霉菌毒素和/或含氨基化合物。因此，从目前的观点来看，不能排除多氯联苯对人类（儿童）造成遗传风险。
