Genotoxicity but not the AhR-mediated activity of PAHs is inhibited by other components of complex mixtures of ambient air pollutants

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• 作者：Helena Lí ; balová ; ^a ; Simona Kr膷ková ; ^b ; Kate艡ina Uhlí ; 艡ová ; ^a ; Alena Milcová ; ^a ; Jana Schmuczerová ; ^a ; Miroslav Ciganek^b ; Jiri Klé ; ma^c ; Miroslav Machala^b ; Radim J. &Scaron ; rá ; m^a ; Jan Topinka^a ; ^{jtopinka@biomed.cas.cz" class="auth_mail}
• 关键词：A549 ; human adenocarcinoma alveolar basal epithelial cells ; type II ; AhR ; aryl hydrocarbon receptor ; B[a]P ; benzo[a]pyrene ; DB[a ; l]P ; dibenzo[a ; l]pyrene ; B[k]F ; benzo[k]fluoranthene ; BPDE ; benzo[a]pyrene diolepoxide ; cDNA ; complementary DNA ; c-PAH ; carcinogenic polycyclic aromatic hydrocarbon ; CYP ; cytochrome P450 ; DCM ; dichloromethane ; DMEM ; Dulbeccó ; s modified Eaglé ; s medium ; DMSO ; dimethylsulfoxide ; EOM ; extractable organic matter ; HEL 12469a ; human embryonic lung fibroblasts ; HPL
• 刊名：Toxicology Letters
• 出版年：21 March, 2014
• 年：2014
• 卷：225
• 期：3
• 页码：350-357
• 全文大小：683 K

文摘

In this study, we compared the genotoxicity and aryl hydrocarbon receptor (AhR)-dependent transcriptional changes of selected target genes in human lung epithelial A549 cells incubated for 24 h, either with extractable organic matter (EOMs) from airborne particles <2.5 渭m (PM2.5) collected at four localities from heavily polluted areas of the Czech Republic or two representative toxic polycyclic aromatic hydrocarbons (PAHs) present in EOMs, benzo[a]pyrene (B[a]P) and benzo[k]fluoranthene (B[k]F). Genotoxic effects were determined using DNA adduct analysis or analysis of expression of selected AhR-related genes involved in bioactivation of PAHs (CYP1A1, CYP1B1) and transcriptional repression (TIPARP). Sampled localities differing in the extent and source of air pollution did not exhibit substantially different genotoxicity. DNA adduct levels induced by three subtoxic EOM concentrations were relatively low (1-5 adducts/10⁸ nucleotides), compared to levels induced by similar concentrations of B[a]P, while B[k]F gave very low DNA adduct levels. Here, we compared genotoxicity and gene deregulation induced by complex mixtures containing PAHs with the effects of the comparable concentrations of individual PAHs. Our results suggested inhibition of formation of B[a]P-induced DNA adducts compared to individual B[a]P, probably attributable to competitive inhibition by other non-genotoxic EOM components. In contrast, induction of AhR target genes appeared not to be antagonized by the components of complex mixtures, as induction of CYP1A1, CYP1B1 and TIPARP transcripts reached maximum levels induced by PAHs.