한국발생생물학회지:발생과생식 (Development and Reproduction)

  • 제25권1호
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  • Pages.15-24
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  • 2021
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  • 2465-9525(pISSN)
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  • 2465-9541(eISSN)
한국발생생물학회 (The Korean Society of Developmental Biology)
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Benzo[a]pyrene Cytotoxicity Tolerance in Testicular Sertoli Cells Involves Aryl-hydrocarbon Receptor and Cytochrome P450 1A1 Expression Deficiencies

  • Kim, Jin-Tac (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University) ;
  • Park, Ji-Eun (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University) ;
  • Lee, Seung-Jin (Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology) ;
  • Yu, Wook-Joon (Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology) ;
  • Lee, Hye-Jeong (Department of Pharmacology, College of Medicine, Dong-A University) ;
  • Kim, Jong-Min (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University)
  • 투고 : 2021.01.09
  • 심사 : 2021.02.01
  • 발행 : 2021.03.31
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초록

Benzo[a]pyrene (B[a]P) is a potent carcinogen and is classified as an endocrine-disrupting chemical. In mammalian testes, Sertoli cells support spermatogenesis. Therefore, if these cells are negatively affected by exposure to xenotoxic chemicals, spermatogenesis can be seriously disrupted. In this context, we evaluated whether mouse testicular TM4 Sertoli cells are susceptible to the induction of cytotoxicity-mediated cell death after exposure to B[a] P in vitro. In the present study, while B[a]P and B[a]P-7,8-diol were not able to induce cell death, exposure to BPDE resulted in cell death. BPDE-induced cell death is accompanied by the activation of caspase-3 and caspase-7. Depolarization of the mitochondrial membrane and cytochrome c release from mitochondria were observed in benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-treated cells. These results indicate that TM4 cells are susceptible to apoptosis in a caspase-dependent manner. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that aryl hydrocarbon receptor (AhR) expression was almost undetectable in TM4 cells and that its expression was not altered after B[a]P treatment. This indicates that TM4 cells are nearly AhR-deficient. In TM4 cells, the CYP1A1 protein and its activity were not present. From these results, it is clear that AhR may be a prerequisite for CYP1A1 expression in TM4 cells. Therefore, TM4 cells can be referred to as CYP1A1-deficient cells. Thus, TM4 Sertoli cells are believed to have a rigid and protective cellular machinery against genotoxic agents. In conclusion, it is suggested that tolerance to B[a]P cytotoxicity is associated with insufficient AhR and CYP1A1 expression in testicular Sertoli cells.

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과제정보

This work was supported by Korea Environment Industry & Technology Institute (KEITI) through the Project (Technology Development Project for Safety Management of Household Chemical Products), funded by Korea Ministry of Environment (MOE) (2020002960008).

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