Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals
Abstract Introduction We examined the correlation between the results of in vitro and in vivo chromosomal damage tests by using in-house data of 18 pharmaceutical candidates that showed positive results in the in vitro chromosomal aberration or micronucleus test using CHL/IU cells, and quantitativel...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-03-01
|
| Series: | Genes and Environment |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s41021-018-0094-3 |
| _version_ | 1831840560529276928 |
|---|---|
| author | Eiji Yamamura Chinami Aruga Shigeharu Muto Nobuyuki Baba Yoshifumi Uno |
| author_facet | Eiji Yamamura Chinami Aruga Shigeharu Muto Nobuyuki Baba Yoshifumi Uno |
| author_sort | Eiji Yamamura |
| collection | DOAJ |
| description | Abstract Introduction We examined the correlation between the results of in vitro and in vivo chromosomal damage tests by using in-house data of 18 pharmaceutical candidates that showed positive results in the in vitro chromosomal aberration or micronucleus test using CHL/IU cells, and quantitatively analyzed them especially in regard to exposure levels of the compounds. Findings Eight compounds showed that the exposure levels [maximum plasma concentration (Cmax) and AUC0-24h] were comparable with or higher than the in vitro exposure levels [the lowest effective (positive) concentration (LEC) and AUCvitro = LEC (μg/mL) × treatment time (h)]. Among them, 3 compounds were positive in the in vivo rodent micronucleus assays using bone marrow cells. For 2 compounds, cytotoxicity might produce false-positive results in the in vitro tests. One compound showed in vitro positive results only in the condition with S9 mix which indicated sufficient concentration of unidentified active metabolite(s) might not reach the bone marrow to induce micronuclei. Conclusion These facts suggested that the in vivo exposure levels being equal to or higher than the in vitro exposure levels might be an important factor to detect in vivo chromosomal damage induced by test chemicals. |
| first_indexed | 2024-12-23T06:13:27Z |
| format | Article |
| id | doaj.art-7c95887db1124b6aa9c4d8479e04addd |
| institution | Directory Open Access Journal |
| issn | 1880-7062 |
| language | English |
| last_indexed | 2024-12-23T06:13:27Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Genes and Environment |
| spelling | doaj.art-7c95887db1124b6aa9c4d8479e04addd2022-12-21T17:57:22ZengBMCGenes and Environment1880-70622018-03-014011710.1186/s41021-018-0094-3Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicalsEiji Yamamura0Chinami Aruga1Shigeharu Muto2Nobuyuki Baba3Yoshifumi Uno4Safety Research Laboratories, Mitsubishi Tanabe Pharma CorporationDiscovery Technology Laboratories, Mitsubishi Tanabe Pharma CorporationSafety Research Laboratories, Mitsubishi Tanabe Pharma CorporationSafety Research Laboratories, Mitsubishi Tanabe Pharma CorporationSafety Research Laboratories, Mitsubishi Tanabe Pharma CorporationAbstract Introduction We examined the correlation between the results of in vitro and in vivo chromosomal damage tests by using in-house data of 18 pharmaceutical candidates that showed positive results in the in vitro chromosomal aberration or micronucleus test using CHL/IU cells, and quantitatively analyzed them especially in regard to exposure levels of the compounds. Findings Eight compounds showed that the exposure levels [maximum plasma concentration (Cmax) and AUC0-24h] were comparable with or higher than the in vitro exposure levels [the lowest effective (positive) concentration (LEC) and AUCvitro = LEC (μg/mL) × treatment time (h)]. Among them, 3 compounds were positive in the in vivo rodent micronucleus assays using bone marrow cells. For 2 compounds, cytotoxicity might produce false-positive results in the in vitro tests. One compound showed in vitro positive results only in the condition with S9 mix which indicated sufficient concentration of unidentified active metabolite(s) might not reach the bone marrow to induce micronuclei. Conclusion These facts suggested that the in vivo exposure levels being equal to or higher than the in vitro exposure levels might be an important factor to detect in vivo chromosomal damage induced by test chemicals.http://link.springer.com/article/10.1186/s41021-018-0094-3GenotoxicityIn vitro-in vivo correlationChromosomal damageExposure level |
| spellingShingle | Eiji Yamamura Chinami Aruga Shigeharu Muto Nobuyuki Baba Yoshifumi Uno Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals Genes and Environment Genotoxicity In vitro-in vivo correlation Chromosomal damage Exposure level |
| title | Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals |
| title_full | Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals |
| title_fullStr | Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals |
| title_full_unstemmed | Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals |
| title_short | Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals |
| title_sort | correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals |
| topic | Genotoxicity In vitro-in vivo correlation Chromosomal damage Exposure level |
| url | http://link.springer.com/article/10.1186/s41021-018-0094-3 |
| work_keys_str_mv | AT eijiyamamura correlationbetweentheresultsofinvitroandinvivochromosomaldamagetestsinconsiderationofexposurelevelsoftestchemicals AT chinamiaruga correlationbetweentheresultsofinvitroandinvivochromosomaldamagetestsinconsiderationofexposurelevelsoftestchemicals AT shigeharumuto correlationbetweentheresultsofinvitroandinvivochromosomaldamagetestsinconsiderationofexposurelevelsoftestchemicals AT nobuyukibaba correlationbetweentheresultsofinvitroandinvivochromosomaldamagetestsinconsiderationofexposurelevelsoftestchemicals AT yoshifumiuno correlationbetweentheresultsofinvitroandinvivochromosomaldamagetestsinconsiderationofexposurelevelsoftestchemicals |