Early-life exposure to benzo[a]pyrene increases mutant frequency in spermatogenic cells in adulthood.
Children are vulnerable to environmental mutagens, and the developing germline could also be affected. However, little is known about whether exposure to environmental mutagens in childhood will result in increased germline mutations in subsequent adult life. In the present study, male transgenic lacI mice at different ages (7, 25 and 60 days old) were treated with a known environmental mutagen (benzo[a]pyrene, B[a]P) at different doses (0, 50, 200 or 300 mg/kg body weight). Mutant frequency was then determined in a meiotic cell type (pachytene spermatocyte), a post-meiotic cell type (round spermatid) and epididymal spermatozoa after at least one cycle of spermatogenesis. Our results show that 1) mice treated with B[a]P at 7 or 25 days old, both being pre-adult ages, had significantly increased mutant frequencies in all spermatogenic cell types tested when they were 60 days old; 2) spermatogenic cells from mice treated before puberty were more susceptible to B[a]P-associated mutagenesis compared to adult mice; and 3) unexpectedly, epididymal spermatozoa had the highest mutant frequency among the spermatogenic cell types tested. These data show that pre-adult exposure to B[a]P increases the male germline mutant frequency in young adulthood. The data demonstrate that exposure to environmental genotoxins at different life phases (e.g., pre-adult and adult) can have differential effects on reproductive health.
Department of Cellular and Structural Biology, the University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Guogang
G
Xu
Department of Pathology, the University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
C Alex
CA
McMahan
Department of Cellular and Structural Biology, the University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Cancer Therapy and Research Center, the University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Barshop Institute for Longevity and Aging Sciences, the University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; South Texas Veteran's Health Care System, San Antonio, Texas, United States of America.
Christi A
CA
Walter
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D012741:Sexual Maturation; D013087:Spermatids / Q000187:drug effects*; D013090:Spermatocytes / Q000187:drug effects*
D009153:Mutagens; D001564:Benzo(a)pyrene