Low concentration of anti‐7,8‐dihydroxy‐9,10‐epoxy‐7,8,9,10‐tetrahydrobenzo[a]pyrene induces alterations of extracellular protein profile of exposed epithelial cells

Abstract

7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) exposure induces adduct formation and oxidative damage on DNA, and consequently triggers complicated stress responses, including such responses as signaling pathway activation, cell cycle arrest, DNA repair, translesion DNA synthesis and mutagenesis. In the present study, 2-DE and MALDI-TOF MS were employed to analyze the differential extracellular protein patterns of human amniotic epithelial cells (FL cells) after exposure to 5 nM BPDE and control. As a result, one protein spot that appeared in the culture medium of BPDE treatment group was successfully identified as 14-3-3zeta, and three up-regulated protein spots were identified as annexin A3, annexin V and hydroxypyruvate isomerase homolog. Among them, 14-3-3zeta was further detected in some pleural fluid specimens also. These results demonstrate that BPDE exposure can induce alterations of extracellular protein profiles of exposed cells, which may be served as a starting point for searching candidate biomarkers for benzo[a]pyrene exposure.

Proteomic Analysis of Cellular Response to Novel Proapoptotic Agents Related to Atypical Retinoids in Human IGROV-1 Ovarian Carcinoma Cells

“…It is also interesting to note that some of the identified proteins were also reported as regulated by genotoxic agents with a mechanism of action different from that of these AR related compounds. For example, 14-3-3 zeta polypeptide, hnRNPs, and the nuclear lamins proteins were also modulated after N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG) exposure , while proteasome subunits proteins were also modulated after 10-alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) treatment. , This suggests that even if different genotoxic agents follow different mechanisms of action, their action may be based on the modulation of some common key proteins involved for example in signal transduction, RNA processing, and cytoskeleton organization.…”

Review on proteomic analyses of benzo[a]pyrene toxicity

“…In another study carried out by same group, the effect of a low BPDE concentration and a short exposure time on the amniotic epithelial cell line FL was analyzed by using 2DE []. The cells were exposed to 5 nM BPDE for a time period of 2.5 h. No significant effect on cell viability was observed at this concentration and exposure time, but a notable alteration in mRNA and protein expression was found.…”

Protein expression profiling in chemical carcinogenesis: A proteomic‐based approach

“…Liu et al 47 analysed differential extracellular protein patterns of human amniotic epithelial cells after short‐term exposure to a metabolite of BaP, 7,8‐dihydroxy‐9,10‐epoxy‐7,8,9,10‐tetrahydrobenzo[a]pyrene (BPDE). They identified three altered protein spots as 14‐3‐3zeta, annexin A3, annexin V, and hydroxypyruvate isomerase homolog.…”

“…The importance of this system is shown by the discussion about proteasome inhibitors as an exciting new strategy for the treatment of cancer. In their third study, human amniotic cells were exposed to 5 nM anti‐7,8‐dihydroxy‐9,10‐epoxy‐7,8,9,10‐tetrahydrobenzo[a]pyrene for 2.5 h 47. Again the cells could recover for 12 h with fresh medium before lysis.…”