Excretion of urinary N7 guanine and N3 adenine DNA adducts in mice after inhalation of styrene

Mikeš, Petr; Kořínek, Marek; Linhart, Igor; Krouželka, Jan; Frantík, E; Vodičková, Ľudmila; Neufussová, Lenka

doi:10.1016/j.toxlet.2008.10.010

Cited by 7 publications

(3 citation statements)

References 25 publications

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“…The researchers concluded that the levels of DNA adducts were detectable in rat liver (nontarget organ), but not in the mouse lung (target organ), thus did not correspond with tumor incidence. Mikeš et al () confirmed formation of N7 ‐SO‐G and α and β N 3‐SO‐A DNA adducts in mouse urine after repeated inhalation exposure to styrene, concluding these adducts were likely rapidly depurinated and eliminated.…”

Section: Critical Review Of the Individual Studies For Styrene/somentioning

confidence: 99%

Critical review of styrene genotoxicity focused on the mutagenicity/clastogenicity literature and using current organization of economic cooperation and development guidance

Moore¹,

Pottenger²,

House‐Knight³

2019

Environ and Mol Mutagen

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Styrene is an important high production volume chemical used to manufacture polymeric products. In 2018, International Agency for Research on Cancer classified styrene as probably carcinogenic to humans; National Toxicology Program lists styrene as reasonably anticipated to be a human carcinogen. The genotoxicity literature for styrene and its primary metabolite, styrene 7,8‐oxide (SO), begins in the 1970s. Organization of Economic Cooperation and Development (OECD) recently updated most genotoxicity test guidelines, making substantial new recommendations for assay conduct and data evaluation for the standard mutagenicity/clastogenicity assays. Thus, a critical review of the in vitro and in vivo rodent mutagenicity/clastogenicity studies for styrene and SO, based on the latest OECD recommendations, is timely. This critical review considered whether a study was optimally designed, conducted, and interpreted and provides a critical assessment of the evidence for the mutagenicity/clastogenicity of styrene/SO. Information on the ability of styrene/SO to induce other types of genotoxicity endpoints is summarized but not critically reviewed. We conclude that when styrene is metabolized to SO, it can form DNA adducts, and positive in vitro mutagenicity/clastogenicity results can be obtained. SO is mutagenic in bacteria and the in vitro mouse lymphoma gene mutation assay. No rodent in vivo mutation studies were identified. SO is clastogenic in cultured mammalian cells. Although the in vitro assays gave positive responses, styrene/SO is not clastogenic/aneugenic in vivo in rodents. In addition to providing updated information for styrene, this review demonstrates the application of the new OECD guidelines for chemicals with large genetic toxicology databases where published results may or may not be reliable. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

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Section: Critical Review Of the Individual Studies For Styrene/somentioning

confidence: 99%

Critical review of styrene genotoxicity focused on the mutagenicity/clastogenicity literature and using current organization of economic cooperation and development guidance

Moore¹,

Pottenger²,

House‐Knight³

2019

Environ and Mol Mutagen

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“…Some studies represent the evidence of SO production and DNA adduct formation induced by inhalation exposure of styrene in vivo [ 54 , 71 , 79 ]. However, it does not mean that these adducts result in the induction of gene mutations.…”

Section: Discussionmentioning

confidence: 99%

In vivo mutagenicity assessment of styrene in MutaMouse liver and lung

Murata

Natsume²,

Iso

et al. 2023

Genes and Environ

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Background Styrene (CAS 100-42-5) is widely used as polystyrene and acrylonitrile–butadiene–styrene resin such as plastic, rubber, and paint. One of the primary uses of styrene is food utensils and containers, but a small amount of styrene transferred into food can be ingested by eating. Styrene is metabolized into styrene 7,8-oxide (SO). SO is mutagenic in bacteria and mouse lymphoma assays. It is clastogenic in cultured mammalian cells. However, styrene and SO are not clastogenic/aneugenic in rodents, and no rodent in vivo gene mutation studies were identified. Methods To investigate the mutagenicity of orally administered styrene, we used the transgenic rodent gene mutation assay to perform an in vivo mutagenicity test (OECD TG488). The transgenic MutaMouse was given styrene orally at doses of 0 (corn oil; negative control), 75, 150, and 300 mg/kg/day for 28 days, and mutant frequencies (MFs) were determined using the lacZ assay in the liver and lung (five male mice/group). Results There were no significant differences in the MFs of the liver and lung up to 300 mg/kg/day (close to maximum tolerable dose (MTD)), when one animal with extremely high MFs that were attributed to an incidental clonal mutation was omitted. Positive and negative controls produced the expected results. Conclusions These findings show that styrene is not mutagenic in the liver and lung of MutaMouse under this experimental condition.

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“…A detecção de adutos de DNA em amostras de sangue ou tecidos de humanos e animais é bastante empregada na literatura. Recentemente, estão sendo desenvolvidas metodologias não invasivas que detectam estes adutos após excreção na urina, que torna a análise mais simples tanto pela disponibilidade de amostras quanto pela extração do aduto da matriz (Meerang et al, 2008;Mikes et al, 2008;Sun et al, 2006).…”

Section: Níveis E Métodos De Detecçãounclassified

Quantificação de danos em DNA induzidos por acetaldeído. Potencial biomarcador de poluição ambiental

García¹

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À FAPESP pelo apoio financeiro e pela bolsa de doutorado. Ao CNPQ, Finep e INCT de processos redox em biomedicina-Redoxoma pelo apoio financeiro À Profa. Dra. Marisa H. G. Medeiros que me aceitou como aluna de iniciação científica quando eu mal sabia o que era DNA e me formou doutora, meu agradecimento e gratidão eternos. Ao Osmar F Gomes, pela amizade, companheirismo, paciência e colaboração de tantos anos. À Profa. Dra. Ana Paula de Melo Loureiro, uma das pessoas mais doces do mundo, que me ensinou desde as primeiras pipetadas até como se portar em um laboratório. À Dra. Sabrina de Almeida Marques, minha também orientadora de Iniciação Cientifica é uma das responsáveis por tudo que me tornei hoje, além de uma excelente amiga a qual sinto muita falta.

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Excretion of urinary N7 guanine and N3 adenine DNA adducts in mice after inhalation of styrene

Cited by 7 publications

References 25 publications

Critical review of styrene genotoxicity focused on the mutagenicity/clastogenicity literature and using current organization of economic cooperation and development guidance

Critical review of styrene genotoxicity focused on the mutagenicity/clastogenicity literature and using current organization of economic cooperation and development guidance

In vivo mutagenicity assessment of styrene in MutaMouse liver and lung

Quantificação de danos em DNA induzidos por acetaldeído. Potencial biomarcador de poluição ambiental

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