Abstract
High doses of Metofluthrin (MTF) have been shown to produce liver tumours in rats by a mode of action (MOA) involving activation of the constitutive androstane receptor leading to liver hypertrophy, induction of cytochrome P450 (CYP) forms and increased cell proliferation. The aim of this study was to compare the effects of MTF with those of the known rodent liver tumour promoter phenobarbital (PB) on the induction CYP2B forms and replicative DNA synthesis in cultured rat and human hepatocytes. Treatment with 50 {mu}M MTF and 50 {mu}M PB for 72 h increased CYP2B1 mRNA levels in male Wistar rat hepatocytes and CYP2B6 mRNA levels in human hepatocytes. Replicative DNA synthesis was determined by incorporation of 5-bromo-2'-deoxyuridine over the last 24 h of a 48 h treatment period. Treatment with 10-1000 {mu}M MTF and 100-500 {mu}M PB resulted in significant increases in replicative DNA synthesis in rat hepatocytes. While replicative DNA synthesis was increased in human hepatocytes treated with 5-50 ng/ml epidermal growth factor or 5-100 ng/ml hepatocyte growth factor, treatment with MTF and PB had no effect. These results demonstrate that while both MTF and PB induce CYP2B forms in both species, MTF and PB only induced replicative DNA synthesis
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Hirose, Yukihiro;
Nagahori, Hirohisa;
[1]
Yamada, Tomoya;
[1]
Deguchi, Yoshihito;
Tomigahara, Yoshitaka;
Nishioka, Kazuhiko;
Uwagawa, Satoshi;
Kawamura, Satoshi;
Isobe, Naohiko;
[1]
Lake, Brian G;
[2]
Centre for Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom)];
Okuno, Yasuyoshi
[1]
- Environmental Health Science Laboratory, Sumitomo Chemical Company Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-8558 (Japan)
- LFI Molecular Sciences, Randalls Road, Leatherhead, Surrey KT22 7RY (United Kingdom)
Citation Formats
Hirose, Yukihiro, Nagahori, Hirohisa, Yamada, Tomoya, Deguchi, Yoshihito, Tomigahara, Yoshitaka, Nishioka, Kazuhiko, Uwagawa, Satoshi, Kawamura, Satoshi, Isobe, Naohiko, Lake, Brian G, Centre for Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom)], and Okuno, Yasuyoshi.
Comparison of the effects of the synthetic pyrethroid Metofluthrin and phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured rat and human hepatocytes.
Ireland: N. p.,
2009.
Web.
doi:10.1016/j.tox.2009.01.007.
Hirose, Yukihiro, Nagahori, Hirohisa, Yamada, Tomoya, Deguchi, Yoshihito, Tomigahara, Yoshitaka, Nishioka, Kazuhiko, Uwagawa, Satoshi, Kawamura, Satoshi, Isobe, Naohiko, Lake, Brian G, Centre for Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom)], & Okuno, Yasuyoshi.
Comparison of the effects of the synthetic pyrethroid Metofluthrin and phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured rat and human hepatocytes.
Ireland.
https://doi.org/10.1016/j.tox.2009.01.007
Hirose, Yukihiro, Nagahori, Hirohisa, Yamada, Tomoya, Deguchi, Yoshihito, Tomigahara, Yoshitaka, Nishioka, Kazuhiko, Uwagawa, Satoshi, Kawamura, Satoshi, Isobe, Naohiko, Lake, Brian G, Centre for Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom)], and Okuno, Yasuyoshi.
2009.
"Comparison of the effects of the synthetic pyrethroid Metofluthrin and phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured rat and human hepatocytes."
Ireland.
https://doi.org/10.1016/j.tox.2009.01.007.
@misc{etde_21181398,
title = {Comparison of the effects of the synthetic pyrethroid Metofluthrin and phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured rat and human hepatocytes}
author = {Hirose, Yukihiro, Nagahori, Hirohisa, Yamada, Tomoya, Deguchi, Yoshihito, Tomigahara, Yoshitaka, Nishioka, Kazuhiko, Uwagawa, Satoshi, Kawamura, Satoshi, Isobe, Naohiko, Lake, Brian G, Centre for Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom)], and Okuno, Yasuyoshi}
abstractNote = {High doses of Metofluthrin (MTF) have been shown to produce liver tumours in rats by a mode of action (MOA) involving activation of the constitutive androstane receptor leading to liver hypertrophy, induction of cytochrome P450 (CYP) forms and increased cell proliferation. The aim of this study was to compare the effects of MTF with those of the known rodent liver tumour promoter phenobarbital (PB) on the induction CYP2B forms and replicative DNA synthesis in cultured rat and human hepatocytes. Treatment with 50 {mu}M MTF and 50 {mu}M PB for 72 h increased CYP2B1 mRNA levels in male Wistar rat hepatocytes and CYP2B6 mRNA levels in human hepatocytes. Replicative DNA synthesis was determined by incorporation of 5-bromo-2'-deoxyuridine over the last 24 h of a 48 h treatment period. Treatment with 10-1000 {mu}M MTF and 100-500 {mu}M PB resulted in significant increases in replicative DNA synthesis in rat hepatocytes. While replicative DNA synthesis was increased in human hepatocytes treated with 5-50 ng/ml epidermal growth factor or 5-100 ng/ml hepatocyte growth factor, treatment with MTF and PB had no effect. These results demonstrate that while both MTF and PB induce CYP2B forms in both species, MTF and PB only induced replicative DNA synthesis in rat and not in human hepatocytes. These results provide further evidence that the MOA for MTF-induced rat liver tumour formation is similar to that of PB and some other non-genotoxic CYP2B form inducers and that the key event of increased cell proliferation would not occur in human liver.}
doi = {10.1016/j.tox.2009.01.007}
journal = []
issue = {1}
volume = {258}
place = {Ireland}
year = {2009}
month = {Apr}
}
title = {Comparison of the effects of the synthetic pyrethroid Metofluthrin and phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured rat and human hepatocytes}
author = {Hirose, Yukihiro, Nagahori, Hirohisa, Yamada, Tomoya, Deguchi, Yoshihito, Tomigahara, Yoshitaka, Nishioka, Kazuhiko, Uwagawa, Satoshi, Kawamura, Satoshi, Isobe, Naohiko, Lake, Brian G, Centre for Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom)], and Okuno, Yasuyoshi}
abstractNote = {High doses of Metofluthrin (MTF) have been shown to produce liver tumours in rats by a mode of action (MOA) involving activation of the constitutive androstane receptor leading to liver hypertrophy, induction of cytochrome P450 (CYP) forms and increased cell proliferation. The aim of this study was to compare the effects of MTF with those of the known rodent liver tumour promoter phenobarbital (PB) on the induction CYP2B forms and replicative DNA synthesis in cultured rat and human hepatocytes. Treatment with 50 {mu}M MTF and 50 {mu}M PB for 72 h increased CYP2B1 mRNA levels in male Wistar rat hepatocytes and CYP2B6 mRNA levels in human hepatocytes. Replicative DNA synthesis was determined by incorporation of 5-bromo-2'-deoxyuridine over the last 24 h of a 48 h treatment period. Treatment with 10-1000 {mu}M MTF and 100-500 {mu}M PB resulted in significant increases in replicative DNA synthesis in rat hepatocytes. While replicative DNA synthesis was increased in human hepatocytes treated with 5-50 ng/ml epidermal growth factor or 5-100 ng/ml hepatocyte growth factor, treatment with MTF and PB had no effect. These results demonstrate that while both MTF and PB induce CYP2B forms in both species, MTF and PB only induced replicative DNA synthesis in rat and not in human hepatocytes. These results provide further evidence that the MOA for MTF-induced rat liver tumour formation is similar to that of PB and some other non-genotoxic CYP2B form inducers and that the key event of increased cell proliferation would not occur in human liver.}
doi = {10.1016/j.tox.2009.01.007}
journal = []
issue = {1}
volume = {258}
place = {Ireland}
year = {2009}
month = {Apr}
}