2-Nitroanisole-induced oxidative DNA damage in Salmonella typhimurium and in rat urinary bladder cells.

Abstract

2-Nitroanisole (2-NA) is used in the manufacturing of azo dyes and causes cancer, mainly in the urinary bladder. Previous in vivo genotoxic data seems to be insufficient to explain the mechanism through which 2-NA induces carcinogenesis, and several bladder carcinogens were reported to induce oxidative DNA damage. Thus, we examined the potential induction of oxidative DNA damage by 2-NA using bacterial strain YG3008, a mutMST-deficient derivative of strain TA100. Consequently, strain YG3008, when compared with strain TA100, was found to be more sensitive to 2-NA, indicating oxidative DNA damage in bacterial cells. For further investigation, we performed the comet assay using the urinary bladder and liver of rats, with and without human 8-oxoguanine DNA-glycosylase 1 (hOGG1), to confirm the potential of 2-NA for inducing oxidative DNA damage. Simultaneously, we conducted a micronucleus test using bone marrow from rats to assess the genotoxicity of 2-NA in vivo. 2-NA was administered orally to male Fischer 344 rats for 3 consecutive days. The rats were divided into 6 treatment groups: 3 groups treated with 2-NA at doses of 125, 250, and 500mg/kg; a group treated with the combination of 2-NA and glutathione-SH (GSH); a negative control group; and a positive control group. The comet assay without hOGG1 detected no DNA damage in the liver or urinary bladder, and the micronucleus test did not show clastogenic effects in bone marrow cells. However, the comet assay with hOGG1 was positive in the urinary bladder samples, indicating the induction of oxidative DNA damage in the urinary bladder for the group treated with 2-NA at 500mg/kg. Moreover, an antioxidant of GSH significantly reduced oxidative DNA damage caused by 2-NA. These results indicate that oxidative DNA damage is a possible mode of action for carcinogenesis in the urinary bladder of rats treated with 2-NA.

• Authors: Kunio Wada, Yoshitaka Katoh, Aya Ohnuma-Koyama, Naofumi Takahashi, Masami Yamada, Kyomu Matsumoto
• Journal: Mutation research. Genetic toxicology and environmental mutagenesis (Mutat Res Genet Toxicol Environ Mutagen) Vol. 816-817 Pg. 18-23 (Apr 2017) ISSN: 1879-3592 [Electronic] Netherlands
• PMID: 28464992 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Anisoles
• Mutagens
• DNA Glycosylases
• oxoguanine glycosylase 1, human
• 2-nitroanisole

Topics

• Animals
• Anisoles (toxicity)
• Comet Assay
• DNA Damage (drug effects)
• DNA Glycosylases (metabolism)
• Liver (drug effects)
• Male
• Micronucleus Tests
• Mutagens (toxicity)
• Oxidation-Reduction
• Rats
• Rats, Inbred F344
• Salmonella typhimurium (drug effects)
• Urinary Bladder (cytology, drug effects)
• Weight Gain