کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2147797 | 1548565 | 2016 | 13 صفحه PDF | دانلود رایگان |
• We report historical control data from the reconstructed skin micronucleus (RSMN) assay.
• True/false positive and negative chemicals were correctly identified.
• 72 h dosing should be conducted to follow up a negative result after 48 h dosing.
• CREST analysis as part of the RSMN assay can distinguish aneugens and clastogens.
• Cytokines release can be used as proliferation and toxicity markers of chemicals.
The in vitro human reconstructed skin micronucleus (RSMN) assay in EpiDerm™ is a promising novel animal alternative for evaluating genotoxicity of topically applied chemicals. It is particularly useful for assessing cosmetic ingredients that can no longer be tested using in vivo assays. To advance the use of this test especially for regulatory decision-making, we have established the RSMN assay in our laboratory according to Good Laboratory Practice and following the principles of the OECD test guideline 487 in vitro mammalian cell micronucleus test. Proficiency with the assay was established by correctly identifying direct-acting genotoxins and genotoxins requiring metabolism, as well as non-genotoxic/non-carcinogenic chemicals. We also report the analysis of our historical control data that demonstrate vehicle control and positive control values for %micronuclei in binucleated cells are in the ranges reported previously. Technical issues including evaluating various solvents with both 48 h and 72 h treatment regimens were investigated. For the first time, mechanistic studies using CREST analysis revealed that the RSMN assay is suitable for distinguishing aneugens and clastogens. Moreover, the assay is also suitable for measuring cytokines as markers for proliferative and toxic effects of chemicals.
Journal: Mutation Research/Genetic Toxicology and Environmental Mutagenesis - Volume 805, July 2016, Pages 25–37