Benzo[a]pyrene Cytotoxicity Tolerance in Testicular Sertoli Cells Involves Aryl-hydrocarbon Receptor and Cytochrome P450 1A1 Expression Deficiencies.

Content Provider	Europe PMC
Author	Kim, Jin-Tac Park, Ji-Eun Lee, Seung-Jin Yu, Wook-Joon Lee, Hye-Jeong Kim, Jong-Min
Copyright Year	2021
Abstract	AbstractBenzo[a]pyrene (B[a]P) is a potent carcinogen and is classified as anendocrine-disrupting chemical. In mammalian testes, Sertoli cells supportspermatogenesis. Therefore, if these cells are negatively affected by exposureto xenotoxic chemicals, spermatogenesis can be seriously disrupted. In thiscontext, we evaluated whether mouse testicular TM4 Sertoli cells are susceptibleto the induction of cytotoxicity-mediated cell death after exposure to B[a]P in vitro. In the present study, while B[a]P andB[a]P-7,8-diol were not able to induce cell death, exposure to BPDE resulted incell death. BPDE-induced cell death is accompanied by the activation ofcaspase-3 and caspase-7. Depolarization of the mitochondrial membrane andcytochrome c release from mitochondria were observed inbenzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-treated cells. These resultsindicate that TM4 cells are susceptible to apoptosis in a caspase-dependentmanner. Western blot and reverse transcription-polymerase chain reaction(RT-PCR) analyses showed that aryl hydrocarbon receptor (AhR) expression wasalmost undetectable in TM4 cells and that its expression was not altered afterB[a]P treatment. This indicates that TM4 cells are nearly AhR-deficient. In TM4cells, 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, TM4Sertoli cells are believed to have a rigid and protective cellular machineryagainst genotoxic agents. In conclusion, it is suggested that tolerance to B[a]Pcytotoxicity is associated with insufficient AhR and CYP1A1 expression intesticular Sertoli cells.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC8087263&blobtype=pdf
ISSN	24659525
Journal	Development & Reproduction [Dev Reprod]
Volume Number	25
PubMed Central reference number	PMC8087263
Issue Number	1
PubMed reference number	33977171
e-ISSN	24659541
DOI	10.12717/dr.2021.25.1.15
Language	English
Publisher	Korean Society of Developmental Biology
Publisher Date	2021-03-31
Access Restriction	Open
Rights License	This is an Open-Access article distributed under the terms of theCreative Commons Attribution Non-Commercial License (http://creative-commons.org/licenses/by-nc/4.0) which permitsunrestricted non-commercial use, distribution, and reproduction in anymedium, provided the original work is properly cited. © Copyright 2021 The Korean Society of DevelopmentalBiology
Subject Keyword	Aryl-hydrocarbon receptor Cytochrome P450 1A1 Benzo[a]pyrene Cytotoxicity Sertoli cells
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry, Genetics and Molecular Biology