Madison T. Stewart , Gu Zhou , Danielle P.M. LeBlanc , Annette E. Dodge , Matthew J. Meier , Andrew Williams , Alexandra S. Long , Paul A. White , Carole L. Yauk , Francesco Marchetti
{"title":"Long term exposure to benzo[b]fluoranthene does not induce mutations in Mutamouse male germ cells","authors":"Madison T. Stewart , Gu Zhou , Danielle P.M. LeBlanc , Annette E. Dodge , Matthew J. Meier , Andrew Williams , Alexandra S. Long , Paul A. White , Carole L. Yauk , Francesco Marchetti","doi":"10.1016/j.reprotox.2025.108985","DOIUrl":null,"url":null,"abstract":"<div><div>Germ cell mutations can be inherited and lead to genetic disorders in the offspring. Thus, it is critical to identify environmental exposures that impact the germline. Polycyclic aromatic hydrocarbons (PAHs) are widespread combustion by-products found in food, tobacco smoke, and urban air. Benzo[<em>b</em>]fluoranthene (BbF) is a PAH that is classified as a possible human carcinogen. Studies using the transgenic mouse <em>lacZ</em> assay and duplex sequencing (DS), an error-corrected sequencing technology, have demonstrated that BbF robustly induces mutations in somatic tissues. However, the mutagenic effects of BbF on germ cells are unknown. We investigated whether long-term exposure to BbF induces mutations in male germ cells. Adult MutaMouse males were orally exposed to BbF in olive oil at doses of 0, 3.25, 6.25, 12.5, 25, or 50 mg/kg body weight per day (BW/day) for 90 days, or to 0, 1.56, 3.125, 6.25, 12.5, or 25 mg/kg BW/day for 180 days. Mutant frequencies were determined using the <em>lacZ</em> assay (n = 8 per group). Control and high dose groups at each time point were then sequenced to detect mutations using DS (n = 6 per group). Neither method detected significant increases in mutations following BbF exposure. Similarly, there was no increase in C:G > A:T transversions at either time point, the main mutation subtype induced by BbF in somatic tissues. These results suggest that BbF or its active metabolites are not present in germ cells at amounts sufficient to cause mutations, and/or DNA damage repair mechanisms in germ cells effectively repair BbF-induced damage.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 108985"},"PeriodicalIF":2.8000,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S089062382500156X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Germ cell mutations can be inherited and lead to genetic disorders in the offspring. Thus, it is critical to identify environmental exposures that impact the germline. Polycyclic aromatic hydrocarbons (PAHs) are widespread combustion by-products found in food, tobacco smoke, and urban air. Benzo[b]fluoranthene (BbF) is a PAH that is classified as a possible human carcinogen. Studies using the transgenic mouse lacZ assay and duplex sequencing (DS), an error-corrected sequencing technology, have demonstrated that BbF robustly induces mutations in somatic tissues. However, the mutagenic effects of BbF on germ cells are unknown. We investigated whether long-term exposure to BbF induces mutations in male germ cells. Adult MutaMouse males were orally exposed to BbF in olive oil at doses of 0, 3.25, 6.25, 12.5, 25, or 50 mg/kg body weight per day (BW/day) for 90 days, or to 0, 1.56, 3.125, 6.25, 12.5, or 25 mg/kg BW/day for 180 days. Mutant frequencies were determined using the lacZ assay (n = 8 per group). Control and high dose groups at each time point were then sequenced to detect mutations using DS (n = 6 per group). Neither method detected significant increases in mutations following BbF exposure. Similarly, there was no increase in C:G > A:T transversions at either time point, the main mutation subtype induced by BbF in somatic tissues. These results suggest that BbF or its active metabolites are not present in germ cells at amounts sufficient to cause mutations, and/or DNA damage repair mechanisms in germ cells effectively repair BbF-induced damage.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.