Elevation of cell proliferation via generation of reactive oxygen species by piperonyl butoxide contributes to its liver tumor-promoting effects in mice

Archives of Toxicology
Masaomi KawaiKunitoshi Mitsumori

Abstract

Piperonyl butoxide (PBO) is a pesticide synergist used with pyrethroids as a domestic insecticide, and it acts as a non-genotoxic hepatocarcinogen in rats and mice. To clarify whether oxidative stress is involved in the liver tumor-promoting effect of PBO in mice, male mice were subjected to two-thirds partial hepatectomy, followed by N-diethylnitrosamine (DEN) treatment, and given a diet containing 0.6% PBO for 25 weeks. The incidences of cytokeratin (CK) 8/18-positive foci, adenomas, and carcinomas significantly increased in the DEN + PBO group compared with the DEN-alone group. The PCNA-positive ratio significantly increased in non-tumor hepatocytes, CK8/18-positive foci and adenomas in the DEN + PBO group compared with the DEN-alone group. PBO increased reactive oxygen species (ROS) production in microsomes but did not change oxidative DNA damage as assessed by 8-hydroxydeoxyguanosine (8-OHdG). In real-time RT-PCR, PBO upregulated the expression of genes related to metabolism, such as Cytochrome P450 1a1, 2a5, and 2b10, and metabolic stress, such as Por and Nqo1, but downregulated Egfr and Ogg1. PBO also increased early response genes downstream of mitogen-activated protein kinase (MAPK), such as c-Myc that is induced by ex...Continue Reading

References

Feb 1, 1994·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·O TakahashiM Yoneyama
Apr 1, 1996·Current Biology : CB·D J Mann, N C Jones
Feb 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·H J HelbockB N Ames
Jun 17, 1998·Free Radical Biology & Medicine·S Puntarulo, A I Cederbaum
Aug 4, 1998·Human & Experimental Toxicology·W H ButlerF J Preiss
Jan 8, 1999·Archives of Toxicology·H OkamiyaM Takahashi
May 7, 2002·EMBO Reports·Moran BenharAlexander Levitzki
Jul 10, 2003·Cell Cycle·Itaru MatsumuraYuzuru Kanakura
Dec 24, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jie LiuMichael P Waalkes
Apr 23, 2004·Molecular Pharmacology·David SiegelDavid Ross
Dec 13, 2006·Toxicologic Pathology·Mitsuyoshi MotoKunitoshi Mitsumori
Feb 1, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jihei NishimuraKunitoshi Mitsumori
Mar 21, 2007·Cancer Biology & Therapy·Alberto J MonteroJean-Pierre J Issa
Jan 30, 2008·Archives of Toxicology·Masako MugurumaKunitoshi Mitsumori
Jul 5, 2008·Cell Biology International·R R PanchukR S Stoika
Aug 30, 2008·Archives of Toxicology·Yasuaki DewaKunitoshi Mitsumori
Nov 6, 2008·Mutation Research·Andrea De Vizcaya-RuizMariano E Cebrian
May 5, 2009·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Athanasios ValavanidisConstantinos Fiotakis
Aug 20, 2009·Toxicologic Pathology·Masaomi KawaiKunitoshi Mitsumori

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Citations

Jan 21, 2010·Archives of Toxicology·Hermann M Bolt, Jan G Hengstler
Jul 26, 2011·Archives of Toxicology·H M BoltJ G Hengstler
Oct 12, 2012·Archives of Toxicology·H M BoltJ G Hengstler
May 4, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jiangbo WangWei Chen
Apr 1, 2014·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Shintaro HaraMakoto Shibutani
Feb 19, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Colin J HendersonCharles Roland Wolf
Feb 2, 2010·The Journal of Toxicological Sciences·Meilan JinKunitoshi Mitsumori
Nov 11, 2010·Free Radical Research·Mikiei TanakaWilliam E Sonntag

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