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UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test

Abstract

We investigated the photo-mutagenicity and photo-genotoxicity of N-dialkylnitrosamines and its mechanisms of UVA activation. With simultaneous irradiation of UVA, photo-mutagenicity of seven N-dialkylnitrosamines was observed in Ames bacteria (Salmonella typhimurium TA1535) in the absence of metabolic activation. Mutagenicity of pre-irradiated N-dialkylnitrosamines was also observed with S. typhimurium hisG46, TA100, TA102 and YG7108 in the absence of metabolic activation. UVA-mediated mutation with N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) decreased by adding either the NO or OH radical scavenger. When superhelical DNA was irradiated with N-dialkylnitrosamines, nicked circular DNA appeared. Ten N-dialkylnitrosamines examined produced strand breaks in the treated DNA in the presence of UVA. The level of single-strand breaks in {phi}X174 DNA mediated by N-nitrosomorpholine (NMOR) and UVA decreased by adding either a radical scavenger or superoxide dismutase. When calf thymus DNA was treated with N-dialkylnitrosamines (NDMA, NDEA, NMOR, N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP)) and UVA, the ratio of 8-oxodG/dG in the DNA increased. Action spectra were obtained to determine if nitrosamine acts as a sensitizer of UVA. Both mutation frequency and NO formation were highest at the absorption maximum of nitrosamines, approximately 340 nm. The plots of NO formation and mutation frequency align with the absorption curve of NPYR, NMOR and  More>>
Authors:
Arimoto-Kobayashi, Sakae; [1]  Sano, Kayoko; Machida, Masaki; Kaji, Keiko; Yakushi, Keiko [1] 
  1. Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima, Okayama 700-8530 (Japan)
Publication Date:
Sep 10, 2010
Product Type:
Journal Article
Resource Relation:
Journal Name: Mutation Research; Journal Volume: 691; Journal Issue: 1-2; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; ALKYL RADICALS; BIOLOGICAL RADIATION EFFECTS; CALVES; DNA; GUANINE; HYDROXYL RADICALS; IRRADIATION; METABOLIC ACTIVATION; MUTAGEN SCREENING; MUTATION FREQUENCY; NITRIC OXIDE; NITROGEN DIOXIDE; NITROSAMINES; OXIDATION; SALMONELLA TYPHIMURIUM; STRAND BREAKS; SUPEROXIDE DISMUTASE; TOXICITY
OSTI ID:
22143025
Country of Origin:
Netherlands
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0027-5107; Other: PII: S0027-5107(10)00195-8; TRN: NL10S4079097725
Availability:
Available from http://dx.doi.org/10.1016/j.mrfmmm.2010.07.002
Submitting Site:
NLN
Size:
page(s) 47-54
Announcement Date:
Oct 31, 2013

Citation Formats

Arimoto-Kobayashi, Sakae, Sano, Kayoko, Machida, Masaki, Kaji, Keiko, and Yakushi, Keiko. UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test. Netherlands: N. p., 2010. Web. doi:10.1016/J.MRFMMM.2010.07.002.
Arimoto-Kobayashi, Sakae, Sano, Kayoko, Machida, Masaki, Kaji, Keiko, & Yakushi, Keiko. UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test. Netherlands. doi:10.1016/J.MRFMMM.2010.07.002.
Arimoto-Kobayashi, Sakae, Sano, Kayoko, Machida, Masaki, Kaji, Keiko, and Yakushi, Keiko. 2010. "UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test." Netherlands. doi:10.1016/J.MRFMMM.2010.07.002. https://www.osti.gov/servlets/purl/10.1016/J.MRFMMM.2010.07.002.
@misc{etde_22143025,
title = {UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test}
author = {Arimoto-Kobayashi, Sakae, Sano, Kayoko, Machida, Masaki, Kaji, Keiko, and Yakushi, Keiko}
abstractNote = {We investigated the photo-mutagenicity and photo-genotoxicity of N-dialkylnitrosamines and its mechanisms of UVA activation. With simultaneous irradiation of UVA, photo-mutagenicity of seven N-dialkylnitrosamines was observed in Ames bacteria (Salmonella typhimurium TA1535) in the absence of metabolic activation. Mutagenicity of pre-irradiated N-dialkylnitrosamines was also observed with S. typhimurium hisG46, TA100, TA102 and YG7108 in the absence of metabolic activation. UVA-mediated mutation with N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) decreased by adding either the NO or OH radical scavenger. When superhelical DNA was irradiated with N-dialkylnitrosamines, nicked circular DNA appeared. Ten N-dialkylnitrosamines examined produced strand breaks in the treated DNA in the presence of UVA. The level of single-strand breaks in {phi}X174 DNA mediated by N-nitrosomorpholine (NMOR) and UVA decreased by adding either a radical scavenger or superoxide dismutase. When calf thymus DNA was treated with N-dialkylnitrosamines (NDMA, NDEA, NMOR, N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP)) and UVA, the ratio of 8-oxodG/dG in the DNA increased. Action spectra were obtained to determine if nitrosamine acts as a sensitizer of UVA. Both mutation frequency and NO formation were highest at the absorption maximum of nitrosamines, approximately 340 nm. The plots of NO formation and mutation frequency align with the absorption curve of NPYR, NMOR and NDMA. A significant linear correlation between the optical density of N-dialkynitrosamines at 340 nm and NO formation in each irradiated solution was revealed by ANOVA. We would like to propose the hypothesis that the N-nitroso moiety of N-dialkylnitrosamines absorbs UVA photons, UVA-photolysis of N-dialkylnitrosamines brings release of nitric oxide, and subsequent production of alkyl radical cations and active oxygen species follow as secondary events, which cause DNA strand breaks, oxidative and alkylative DNA damages and mutation.}
doi = {10.1016/J.MRFMMM.2010.07.002}
journal = {Mutation Research}
issue = {1-2}
volume = {691}
journal type = {AC}
place = {Netherlands}
year = {2010}
month = {Sep}
}