Ortiz Isabel C, Peláez Carlos A, Orozco Luz Yaneth, Zuleta Margarita
Grupo de Biología de Sistema, Universidad Pontificia Bolivariana, Medellín, Colombia.
Biomedica. 2012 Sep;32(3):437-48. doi: 10.1590/S0120-41572012000300014.
Mutagens contained in complex mixtures can present synergistic interactions, either additive or antagonistic. Therefore, development of experimental approaches is necessary to elucidate which is the responsible agent for the effect in the mixtures.
An experimental design was developed that allowed an understanding of the processes between the compounds of complex mixtures.
Human lymphocytes were exposed to binary mixtures of the mutagens B[a]P, DMBA, Trp-P-1 and MX for 1 hour with or without S9. Viability was assessed with trypan blue dye and the genotoxicity by the comet assay.
All of the hydrocarbon showed an effect with furanone. With and without S9, the most toxic interactions were observed between hydrocarbons. Synergistic interaction was observed without S9 between B [a] P and Trp-P-1 and between DMBA and Trp-P-1 with metabolic activity. Without S9 antagonistic interaction was observed only between Trp-P-1+DMBA, and with S9 between Trp-P-1+MX and MX+DMBA. It observed an increase dose dependent in tail length. Half the cultures showed genotoxic damage and increased cell damage. For each mixture, minimum concentrations were determined at which adverse effects are observed; for some only the maximum concentration was determined at which no adverse effects are observed.
The processes between mutagens present in a mixture have become better understood, and the results validated an analytical model that determined which component had an effect on another. The results also showed that the type of compounds in the mixture determined whether or not a risk threshold was present.
复杂混合物中含有的诱变剂可能呈现协同相互作用,包括相加或拮抗作用。因此,有必要开发实验方法来阐明混合物中产生效应的责任因子。
开发一种实验设计,以了解复杂混合物中化合物之间的相互作用过程。
将人类淋巴细胞暴露于诱变剂苯并[a]芘、二甲基苯蒽、色氨酸-P-1和MX的二元混合物中1小时,有无S9代谢活化系统。用台盼蓝染料评估细胞活力,用彗星试验评估遗传毒性。
所有碳氢化合物与呋喃酮均显示出效应。无论有无S9代谢活化系统,碳氢化合物之间观察到的毒性相互作用最强。在无S9代谢活化系统时,苯并[a]芘与色氨酸-P-1之间以及二甲基苯蒽与色氨酸-P-1之间观察到协同相互作用;在有S9代谢活化系统时,色氨酸-P-1与MX之间以及MX与二甲基苯蒽之间观察到拮抗相互作用。观察到尾长呈剂量依赖性增加。半数培养物显示出遗传毒性损伤和细胞损伤增加。对于每种混合物,确定了观察到不良反应的最低浓度;对于某些混合物,仅确定了未观察到不良反应的最高浓度。
混合物中诱变剂之间的相互作用过程已得到更好的理解,结果验证了一种分析模型,该模型确定了哪种成分对另一种成分有影响。结果还表明,混合物中化合物的类型决定了是否存在风险阈值。