{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T08:22:49Z","timestamp":1783498969033,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"1-2","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Styrene has been shown to induce lung tumors in mice, but not in rats. The current study investigated the potential role of genotoxicity as an initial key event in the mode of action for styrene\u2010induced lung tumors in mice. Transgenic male B6C3F1 Big Blue\u00ae mice were treated by oral gavage for 28 consecutive days with 0 (corn oil), 75, 150, or 300\u2009mg\/kg\/day of styrene. The 300\u2009mg\/kg\/day represented the tumorigenic dose in the oral gavage carcinogenicity study conducted in B6C3F1 mice. Following a 28\u2010day expression period, mutant frequencies were assessed at the <jats:italic>cII<\/jats:italic> locus of the transgene in the tumor target (lung) and non\u2010target tissues (liver, glandular stomach, and duodenum). Mice treated with <jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (40\u2009mg\/kg\/day) by oral gavage on Days 1, 2, and 3 of the study and sacrificed on Day 56 served as the positive control group. Genomic DNA was extracted from the selected tissues, processed for the recovery of the transgene into infectious phage, plated onto <jats:italic>Escherichia coli<\/jats:italic> strain G1250, and incubated at 37\u00b0C for titer determination or at 24\u00b0C for the selection of mutant plaques. There were no treatment\u2010related increases in mutant frequency in any of the tissues. The positive control group had a significant increase in the frequency of <jats:italic>cII<\/jats:italic> mutants assuring the adequacy of the experimental conditions to detect induced mutations. To conclude, mutagenicity is not considered a plausible initial key event in the mode of action for styrene\u2010induced mouse lung tumors as these data support that styrene is not an in vivo mutagen.<\/jats:p>","DOI":"10.1002\/em.22638","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T09:20:10Z","timestamp":1731662410000},"page":"34-44","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation of mutagenicity of styrene in tumor target and non\u2010target tissues of transgenic Big Blue\u00ae mice"],"prefix":"10.1002","volume":"66","author":[{"given":"B. 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