Benzo(a)pyrene Is Mutagenic in Mouse Spermatogonial Stem Cells and Dividing Spermatogonia

• Published in: Toxicological sciences 2016-08, Vol.152 (2), p.363-371
• Main Authors: O'Brien, Jason M, Beal, Marc A, Yauk, Carole L, Marchetti, Francesco
• Format: Article
• Language: English
• Subjects: Animals; Benzo(a)pyrene - toxicity; Cell Division - drug effects; Dose-Response Relationship, Drug; Lac Operon; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mutagenic Effects of Benzo(a)pyrene in Mouse Sperm Stem Cells; Mutagens - toxicity; Spermatogonia - cytology; Spermatogonia - drug effects; Stem Cells - drug effects
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfw088

Although many environmental agents are established male germ cell mutagens, few are known to induce mutations in spermatogonial stem cells. Stem cell mutations are of great concern because they result in a permanent increase in the number of mutations carried in sperm. We investigated mutation induction during mouse spermatogenesis following exposure to benzo(a)pyrene (BaP). MutaMouse males were given 0, 12.5, 25, 50, or 100 mg/kg bw/day BaP for 28 days by oral gavage. Germ cells were collected from the cauda epididymis and seminiferous tubules 3 days after exposure and from cauda epididymis 42 and 70 days after exposure. This design enabled targeted investigation of effects on post-spermatogonia, dividing spermatogonia, and spermatogonial stem cells, respectively. BaP increased lacZ mutant frequency (MF) in cauda sperm after exposure of dividing spermatogonia (4.2-fold at highest dose, P