RGD Reference Report - Threshold dose of piperonyl butoxide that induces reactive oxygen species-mediated hepatocarcinogenesis in rats. - Rat Genome Database

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Threshold dose of piperonyl butoxide that induces reactive oxygen species-mediated hepatocarcinogenesis in rats.

Authors: Muguruma, M  Kawai, M  Dewa, Y  Nishimura, J  Saegusa, Y  Yasuno, H  Jin, M  Matsumoto, S  Takabatake, M  Arai, K  Mitsumori, K 
Citation: Muguruma M, etal., Arch Toxicol. 2008 Jul 22.
RGD ID: 2301056
Pubmed: PMID:18648771   (View Abstract at PubMed)
DOI: DOI:10.1007/s00204-008-0340-8   (Journal Full-text)

To determine the threshold dose of piperonyl butoxide (PBO) that induces hepatocellular tumor-promoting effects, reactive oxygen species (ROS) generation, and drug-metabolizing enzymes that protect against ROS generation, partial hepatectomized rats were fed diets containing 0, 0.015, 0.03, 0.06, 0.125, 0.25, or 0.5% PBO after an i.p. injection of N-diethylnitrosamine (DEN) to initiate hepatocarcinogenesis. Histopathologically, Glutathione S-transferase placental form (GST-P)-positive foci were significantly increased in a dose-dependent manner in rats given 0.25% PBO or higher. The formation of microsomal ROS in the liver was significantly increased in 0.25 and 0.5% PBO. Real-time RT-PCR showed that the expression of the CYP1A1, UDPGTr-2, and Mrp3 genes was significantly upregulated in rats given 0.03% PBO or higher. These results suggest that 0.25% is the threshold dose of PBO that induces ROS-mediated hepatocarcinogenesis in rats, although the CYP1A1 gene that is related to ROS generation and the UDPGTr-2 and Mrp3 genes that are involved in protection against ROS were induced in the livers of rats even at a PBO dose of 0.03%.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to organic cyclic compound  IEP 2301056 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc3  (ATP binding cassette subfamily C member 3)


Additional Information