Increase of somatic cell mutations in oxidative damage-sensitive drosophila

Abstract

BackgroundOxidative damage is an important genotoxic source for almost all organisms. To efficiently detect mutations induced by oxidative damage, we previously developed a urate-null Drosophila strain. Using this Drosophila strain, we showed the mutagenic activity of environmental cigarette smoke (ECS) and the herbicide paraquat, which are known to produce reactive oxygen species (ROS). In the present study, we examined the mutagenic activities of carcinogenic mutagens that are considered to cause mutations by adduct formation, alkylation, or crosslinking of cellular DNA in the oxidative damage-sensitive Drosophila to evaluate how the oxidative damage induced by these mutagens is involved in causing mutations. In addition, we evaluated whether these oxidative damage-sensitive flies may be useful for mutation assays.MethodsWe performed the wing-spot test in oxidative damage-sensitive Drosophila (urate-null strains) to examine the mutagenicity of 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx), mitomycin C (MMC), 4-nitroquinoline N-oxide (4NQO), N-nitrosodimethyl-amine (NDMA), and N-nitrosodiethylamine (NDEA). We also observed the mutagenicity of X-ray irradiation as a control in which mutations should be mainly caused by oxidative damage.ResultsAs expected, the mutagenic activity of X-ray irradiation was higher in the urate-null Drosophila than in the wild-type Drosophila. The mutagenic activities of the tested compounds were also higher in the urate-null Drosophila than in the wild-type Drosophila. In experiments using another urate-null strain, the mutagenicity of N-nitrosodialkylamines was also higher in the urate-null flies than in the wild-type ones.ConclusionsThe tested compounds in this study were more mutagenic in urate-null Drosophila than in wild-type Drosophila. It was supposed that ROS were generated and that the ROS might be involved in mutagenesis. The present results support the notion that in addition to causing DNA lesions via adduct formation, alkylation, or DNA crosslinking, these mutagens also cause mutations via ROS-induced DNA damage. As such, urate-null Drosophila appear to be useful for detecting the mutagenic activity of various mutagens, especially those that produce reactive oxygen. If the mutation rate increases on a mutation assay using urate-null Drosophila, it might suggest that the mutagen generates ROS, and that the produced ROS is involved in causing mutations.

Epanorin, a lichen secondary metabolite, inhibits proliferation of MCF-7 breast cancer cells

“…The lack of mutagenic activity further supports that apoptosis is not a mechanism for the inhibition of MCF-7 cells growth, since mutated cells will normally go into apoptosis. Moreover, ROS were not detected on cells exposed to EP, which is also consistent with EP’s absence of mutagenic activity, since ROS are recognized for their mutagenic activity [16, 36].…”

In vitro and in vivo low-dose exposure of simulated cooking oil fumes to assess adverse biological effects

“…PhIP might be generating ROS by more than one mechanism, which would induce DNA damage and cell toxicity 39 . ROS was generated from MeIQx and the ROS might be involved in mutagenesis 40 . An early study demonstrated that TDA can lead to cytotoxicity and oxidative DNA damage through the induction of ROS at concentrations from 50 to 200 μM in A549 cells 41 .…”

Low-dose biological adverse effects assessment in vitro and in vivo to heterocyclic aromatic amines and aldehydes from cooking oil fumes

“…PhIP might be generating ROS by more than one mechanism, which will induce DNA damage and cell toxicity 38 . ROS was generated from MeIQx and the ROS might be involved in mutagenesis 39 . An early study demonstrated that TDA can lead to cytotoxicity and oxidative DNA damage through the induction of ROS at concentrations from 50-200 µM in A549 cells 40 .…”