Differential effects of polycyclic aromatic hydrocarbons on transactivation of AP-1 and NF-κB in mouse epidermal cl41 cells

✍ Scribed by Jingxia Li; Haobin Chen; Qingdong Ke; Zhaohui Feng; Moon-Shong Tang; Bingci Liu; Shantu Amin; Max Costa; Chuanshu Huang

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 394 KB
• Volume: 40
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20020

✦ Synopsis

Abstract

Polycyclic aromatic hydrocarbons (PAHs) and their derivatives, such as benzo[a]pyrene (B[a]P), (±)‐anti‐benzo[a]pyrene‐7,8‐diol‐9,10‐epoxide (B[a]PDE), and 5‐methylchrysene‐1,2‐diol‐3,4‐epoxide (5‐MCDE), are complete carcinogens. However, the tumor promotion effects of PAHs remain unclear. We therefore investigated the possible activation of activator protein‐1 (AP‐1) and nuclear factor‐κB (NFκB) in mouse epidermal Cl41 cells after different PAHs treatments, including B[a]P, B[a]PDE, chrysene‐1,2‐diol‐3,4‐epoxid (CDE), and 5‐MCDE. The results showed that B[a]PDE and 5‐MCDE were able to activate AP‐1 and NF‐κB, whereas B[a]P showed only marginal effect on AP‐1 activation, and B[a]P and CDE had no effect on NF‐κB activation. Treatment with either B[a]PDE or 5‐MCDE also resulted in mitogen‐activated protein kinases (MAPKs) activation as well as inhibitory subunit kappa‐B (IκBα) phosphorylation and degradation, whereas B[a]P and CDE had no effect. Pretreatment with PD98059, a specific inhibitor for extracellular signal‐regulated protein kinases (ERKs) upstream kinase MEK1/2, or SB202190, a p38 kinase inhibitor, resulted in a dramatic inhibition of B[a]PDE‐induced AP‐1 transactivation. In addition, B[a]PDE‐induced AP‐1 activation was also inhibited by overexpressing a dominant negative mutant of JNK1 in the cells. All these suggest ERKs, c‐jun N‐terminal kinases (JNKs), and p38 kinase signal transduction pathways are required for AP‐1 induction by B[a]PDE. Taken together, B[a]PDE and 5‐MCDE are the active compounds of PAHs to initiate signaling pathways. Considering the important roles of AP‐1 and NF‐κB in tumor promotion, we speculated the activation of AP‐1 and NF‐κB by B[a]PDE and 5‐MCDE may involve in their or their parent compounds' tumor promotion effects. This study may help in better understanding the tumor promotion effects of PAHs. © 2004 Wiley‐Liss, Inc.