A review of the genotoxic potential of 1,4-naphthoquinone

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis Vol. 834; pp. 6 - 17
• Main Authors: Fowler, Paul, Meurer, Krista, Honarvar, Naveed, Kirkland, David
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2018
• Subjects: 1,4-Naphthoquinone; Genotoxicity in vitro; Genotoxicity in vivo; PBS; MN; TFT; 1,4-Naphthoquinone; Hprt; Genotoxicity in vitro; G-6-P; NAD; DMEM; 6-TG; PCE; SCE; 1,4-NQ; tk; ROS; FCS; Genotoxicity in vivo; GSH; CA; BrdU; MoA
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2018.07.004

•1,4-NQ is a commonly used industrial intermediate.•There is no evidence of gene mutation induction in mammalian or bacterial cells.•It does induce clastogenicity in mammalian cells in vitro.•It is however negative for clastogenicity in vivo (mouse and hamster).•Mechanistic data suggests an MoA based on ROS and topoisomerase II inhibition. 1,4-Naphthoquinone (1,4-NQ; CAS RN 130-15-4), a derivative of naphthalene, is a commonly used pre-cursor in industrial processes. Since the early 1980’s 1,4-NQ has been tested in a number of genotoxicity assays, both in vitro and in vivo. There is strong evidence that 1,4-NQ does not induce gene mutations in bacteria or mammalian cells in vitro with predominantly negative Ames tests and negative Hprt and tk mutation studies. However, there is clear evidence of a clastogenic response in vitro from positive micronucleus, sister chromatid exchange and chromosome aberration assays. 1,4-NQ-treated mice and hamsters were, however, negative for micronucleus or chromosomal aberration induction in GLP-compliant studies with clear evidence of target tissue exposure, suggesting an in vitro only effect. Evidence indicates that the mechanism of in vitro clastogenicity is predominantly via ROS generation, and since in vitro mammalian cell tests systems have poor anti-oxidant defence mechanisms, they are particularly sensitive to oxidative DNA damage. On the other hand, healthy mammalian tissues have more efficient anti-oxidant defence mechanisms, and therefore it is not surprising that 1,4-NQ is not genotoxic in vivo.