Tissue distribution of cytochrome P450 3A (CYP3A) in brushtail possums (Trichosurus vulpecula) exposed to Eucalyptus terpenes

Abstract

We evaluated the distribution pattern of a specific xenobiotic metabolizing enzyme, cytochrome P450 3A (CYP3A) in the common brushtail possum (Trichosurus vulpecula). Western blot studies using CYP3A antibodies were used to compare CYP3A levels in the intestine, liver, kidney, brain, testes and adrenal gland in possums fed diets with and without a mixture of terpenes. Possums appear to produce at least 3 different CYP3A-like isoforms that are differentially expressed in various tissues. The liver and duodenum produce all three isoforms (CYP3A P1, P2, P3), the jejunum only produces CYP3A P1, the ileum, kidney, testes and adrenal only produce CYP3A P2 and the brain only produces CYP3A P3. Terpene treatment did not alter relative levels of isoforms present in any tissue type. This study is the first to identify the presence and differential expression of several CYP3A-like isoforms in a variety of tissues of a wild mammalian herbivore. Data suggest that CYP3A-like enzymes are not induced by terpenes. However, the wide distribution of CYP3A-like isoforms in a variety of tissues, suggests that these enzymes are an important mechanism for metabolism in possums and may contribute to the high tolerance possums have to a wide range of xenobiotics.