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Epidemiology:
doi: 10.1097/01.ede.0000276432.92433.12
ISEE 2007 CONFERENCE ABSTRACTS SUPPLEMENT: Abstracts

The Possible Mechanism of Tetrachlorohydroquinone-Induced Apoptosis and Tumor Promotion in NIH3T3 Cells

Wang, Y J; Yang, M C

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Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, Tainan, Taiwan.

ISEE-109

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Objective:

Pentachlorophenol (PCP) and its salt are used extensively as biocide and wood preservative. Because of improper disposal, PCP has become an environmental pollutant and is considered to be ubiquitous. Tetrachlorohydroquinone (TCHQ) is the major toxic metabolite of PCP. Recently, we found that TCHQ was a tumor promoter in a mouse skin carcinogenesis model. However, the detail mechanism of TCHQ-induced tumor promotion is still not clear. In this study, we intended to discover the role of Bcl-2 in TCHQ-induced apoptosis and its related possible signaling pathways in NIH3T3 cells.

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Material and Methods:

DNA fragmentation assay was used to characterize apoptosis in NIH3T3 cells. Flow cytometry analysis was performed to quantify apoptotic cells and intracellular ROS levels. Western blotting analysis was applied to investigate the molecular basis for the effects of TCHQ in NIH3T3 cells.

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Results:

Over-expression of Bcl-2 effectively suppresses TCHQ-induced apoptosis in NIH3T3 cells, as evidenced by morphologic changes and DNA fragmentation. Although production of reactive oxygen species (ROS) contributes to TCHQ-induced apoptosis, Bcl-2 fails to attenuate TCHQ-elicited increase of intracellular ROS level. In addition, over-expressed Bcl-2 provides only partial protection against TCHQ-induced cellular DNA damage. Interestingly, TCHQ induced a significant up-regulation of Bcl-2 expression, and over-expressed Bcl-2 can inhibit TCHQ-induced apoptosis. We also found that TCHQ increased ATM protein expression, but did not induce downstream p53 accumulation and Bax up-regulation. In addition, TCHQ induced expression of both phospho-p38 and phospho-JNK, which belong to MAPK cascade pathway.

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Conclusions:

These data indicate that Bcl-2 prevents TCHQ-induced apoptosis at the downstream of oxidative damage events. The possible signaling pathway of TCHQ-induced apoptosis may relate to MAPK pathway instead of ATM-dependent pathway. Taken together, we suggest that chronic exposure of TCHQ could facilitate the process of tumor promotion through induction of Bcl-2 expression and subsequent apoptosis inhibition.

© 2007 Lippincott Williams & Wilkins, Inc.

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