title: Potential new targets involved in 1,3-dinitrobenzene induced testicular toxicity.
abstract: 1,3-Dinitrobenzene (DNB) causes testicular injury, particularly to Sertoli cells, and induces apoptosis in the surrounding germinal cells in rodents; however, the mechanisms causing this toxicity are poorly understood. Our studies, using standard and molecular tools, were conducted to better understand the pathogenesis of the testicular effects. Four daily oral doses of 0.1-8mg/kg/day caused marked testicular lesions in rats from 4mg/kg/day. Global transcriptomics revealed cell cycle and cell death as the major biological processes affected with the expression of genes associated with cell cycle progression ("mitotic roles of polo-like kinase") being particularly altered. In a single dose time course study (4mg/kg), no adverse changes were recorded; however, in contrast to the data from the multiple dose study, plasma testosterone and testicular steroidogenesis-related gene expression were affected. These steroid hormone effects were confirmed in vitro using the H295R steroidogenesis assay. With this global approach we show that DNB not only induces apoptosis and interferes with cell cycle in the testes but that DNB can also modulate steroid hormone biosynthesis, suggesting an interference with the endocrine system. However, the contribution of the endocrine changes to the severe testicular lesions is presently unknown and requires further investigation.
authors: Bayer SAS, Department of Research Toxicology, 355 rue Dostoïevski, 06903 Sophia-Antipolis, France.
authors: Sophie
authors: S
authors: Ludwig
authors: Helen
authors: H
authors: Tinwell
authors: David
authors: D
authors: Rouquié
authors: Frédéric
authors: F
authors: Schorsch
authors: Marc
authors: M
authors: Pallardy
authors: Rémi
authors: R
authors: Bars
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004136:Dinitrobenzenes / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D011374:Progesterone / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D004136:Dinitrobenzenes; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol