RGD Reference Report - Sex difference in the principal cytochrome P-450 for tributyltin metabolism in rats. - Rat Genome Database

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Sex difference in the principal cytochrome P-450 for tributyltin metabolism in rats.

Authors: Ohhira, Shuji  Enomoto, Mitsunori  Matsui, Hisao 
Citation: Ohhira S, etal., Toxicol Appl Pharmacol. 2006 Jan 1;210(1-2):32-8. doi: 10.1016/j.taap.2005.06.013. Epub 2005 Jul 21.
RGD ID: 401965478
Pubmed: PMID:16039681   (View Abstract at PubMed)
DOI: DOI:10.1016/j.taap.2005.06.013   (Journal Full-text)

Tributyltin is metabolized by cytochrome P-450 (CYP) system enzymes, and its metabolic fate may contribute to the toxicity of the chemical. In the present study, it is examined whether sex differences in the metabolism of tributyltin exist in rats. In addition, the in vivo and in vitro metabolism of tributyltin was investigated using rat hepatic CYP systems to confirm the principal CYP involved. A significant sex difference in metabolism occurred both in vivo and in vitro, suggesting that one of the CYPs responsible for tributyltin metabolism in rats is male specific or predominant at least. Eight cDNA-expressed rat CYPs, including typical phenobarbital (PB)-inducible forms and members of the CYP2C subfamily, were tested to determine their capability for tributyltin metabolism. Among the enzymes studied, a statistically significant dealkylation of tributyltin was mediated by CYP2C6 and 2C11. Furthermore, the sex difference in metabolism disappeared in vitro after anti-rat CYP2C11 antibody pretreatment because CYP2C11 is a major male-specific form in rats. These results indicate that CYP2C6 is the principal CYP for tributyltin metabolism in female rats, whereas CYP2C11 as well as 2C6 is involved in tributyltin metabolism in male rats, and it is suggested that CYP2C11 is responsible for the significant sex difference in the metabolism of tributyltin observed in rats.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cyp2c6Ratxenobiotic catabolic process  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp2c6  (cytochrome P450, family 2, subfamily C, polypeptide 6)


Additional Information