RGD Reference Report - Threshold dose of liver tumor promoting effect of beta-naphthoflavone in rats. - Rat Genome Database

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Threshold dose of liver tumor promoting effect of beta-naphthoflavone in rats.

Authors: Hayashi, H  Taniai, E  Morita, R  Yafune, A  Suzuki, K  Shibutani, M  Mitsumori, K 
Citation: Hayashi H, etal., J Toxicol Sci. 2012;37(3):517-26.
RGD ID: 7296954
Pubmed: PMID:22687991   (View Abstract at PubMed)

To determine the threshold dose of beta-Naphthoflavone (BNF) that induces hepatocellular tumor promoting effects, reactive oxygen species (ROS) generation and thiobarbituric acid-reactive substance (TBARS) formation, and drug-metabolizing enzymes that protect against ROS generation, two-stage liver carcinogenesis model was used. Partial hepatectomized rats (n = 11 to 12) were fed diets containing 0, 0.03, 0.06, 0.125 or 0.25% BNF for 6 weeks after an intraperitoneal injection of N-diethylnitrosamine (DEN) to initiate hepatocarcinogenesis. Histopathologically, glutathione S-transferase placental form (GST-P)-positive foci significantly increased in rats given 0.25% BNF. No marked changes in ROS production and TBARS contents were observed between the BNF treated and DEN alone groups. Real-time RT-PCR showed that the expression of Cyp1a1, Cyp1a2, Cyp1b1 and Nqo1 significantly increased in the groups given 0.03% BNF or more, but Ugt1a6, Akr7a3 and Gstm1 significantly increased in the groups given 0.125% BNF or more. Gpx2 and Yc2 significantly increased in the groups given 0.06% BNF or more and 0.25% BNF, respectively. Inflammation-related genes such as Ccl2, Mmp12, Serpine1 and Cox-2 significantly increased in the 0.25% BNF group. In immunohistochemistry, the number of cyclooxygenase-2 (COX-2)-positive cells increased in rats given 0.25% BNF. These results suggest that 0.25% BNF is the threshold dose for liver tumor promotion, and the fact that inflammation-related genes and COX-2 protein increased in the 0.25% BNF group strongly suggests that inflammation is involved in the liver tumor promoting effect of BNF in rats.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Neoplasms  ISOCyp1a1 (Rattus norvegicus)7296954; 7296954mRNA:increased expression:liverRGD 
Experimental Liver Neoplasms  IEP 7296954mRNA:increased expression:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp1a1  (cytochrome P450, family 1, subfamily a, polypeptide 1)

Genes (Mus musculus)
Cyp1a1  (cytochrome P450, family 1, subfamily a, polypeptide 1)

Genes (Homo sapiens)
CYP1A1  (cytochrome P450 family 1 subfamily A member 1)


Additional Information