Bauer Alison K, Romo Deedee, Friday Finnegan, Cho Kaila, Velmurugan Kalpana, Upham Brad L
Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA.
Toxics. 2024 Dec 2;12(12):882. doi: 10.3390/toxics12120882.
The World Health Organization has classified air pollution as a carcinogen, and polycyclic aromatic hydrocarbons (PAHs) are major components of air particulates of carcinogenic concern. Thus far, most studies focused on genotoxic high molecular weight PAHs; however, recent studies indicate potential carcinogenicity of the non-genotoxic lower molecular weight PAHs (LMW PAHs) that are found in indoor and outdoor air pollution as well as secondhand cigarette smoke. We hypothesize that LMW PAHs contribute to the promotion stage of cancer when combined with benzo[]pyrene (B[]P), a legacy PAH. We specifically determined the effects of an LMW PAH mixture containing 1-methylanthracene (1MeA), fluoranthene (Flthn), and phenanthrene (Phe) combined with B[]P on lung tumor promotion. To test this hypothesis, we used a two-stage, initiation/promotion BALB/ByJ female lung tumor mouse model. The mice were initiated with 3-methylcholanthrene followed by exposures to B[]P, the LMW PAH mixture, and the combination of the LMW PAH mixture plus B[]P, all at 10 mg/kg. The LMW PAHs combined with B[]P significantly increased the promotion and incidence of lung tumors over that of B[]P alone. The LMW PAHs in the absence of B[]P did not significantly promote tumors, indicating strong co-promotional activities. We further assessed the effects of these PAHs on other hallmarks of cancer, namely, bronchoalveolar lavage fluid inflammatory infiltrates, pro-inflammatory transcripts, KC protein content, and mRNA expression of the gap junction () and epiregulin () genes. The LMW PAHs increased the biomarkers of inflammation, decreased expression, and increased expression, all consistent with tumor promotion. This study indicates that non-genotoxic LMW PAHs can contribute to the cancer process and warrants further studies to assess the carcinogenic risks of other LMW PAHs.
世界卫生组织已将空气污染列为致癌物，多环芳烃（PAHs）是具有致癌风险的空气颗粒物的主要成分。到目前为止，大多数研究集中在具有基因毒性的高分子量PAHs上；然而，最近的研究表明，在室内外空气污染以及二手烟中发现的非基因毒性低分子量PAHs（LMW PAHs）也具有潜在致癌性。我们假设，LMW PAHs与遗留PAH苯并[a]芘（B[a]P）结合时，会促进癌症的发展阶段。我们具体测定了含有1-甲基蒽（1MeA）、荧蒽（Flthn）和菲（Phe）的LMW PAH混合物与B[a]P结合对肺肿瘤促进作用的影响。为了验证这一假设，我们使用了两阶段启动/促进的BALB/ByJ雌性肺肿瘤小鼠模型。小鼠先用3-甲基胆蒽启动，然后分别暴露于B[a]P、LMW PAH混合物以及LMW PAH混合物加B[a]P的组合中，剂量均为10 mg/kg。与单独使用B[a]P相比，LMW PAHs与B[a]P结合显著增加了肺肿瘤的促进作用和发病率。在没有B[a]P的情况下，LMW PAHs并没有显著促进肿瘤，表明其具有很强的协同促进活性。我们进一步评估了这些PAHs对癌症其他特征的影响，即支气管肺泡灌洗液中的炎性浸润、促炎转录本、KC蛋白含量以及缝隙连接蛋白（Cx）和表皮调节素（Ereg）基因的mRNA表达。LMW PAHs增加了炎症生物标志物，降低了Cx表达，并增加了Ereg表达，所有这些都与肿瘤促进作用一致。这项研究表明，非基因毒性的LMW PAHs可促进癌症进程，值得进一步研究以评估其他LMW PAHs的致癌风险。
