Cytochrome P450 expression, induction, and activities in the tongue

Human cytochrome P450 enzymes play an important role in the metabolism of numerous endogenous and exogenous compounds. One of the functions of the enzymes is to rid the body of foreign chemicals. However, the metabolism of these chemicals can frequently produce toxic metabolites, which in many instances have been implicated in tumor promotion. The tongue is an organ in the body that experiences high levels of exposure to foreign chemicals, yet has not received much attention in terms of characterization of cytochrome P450 expression. Therefore, the objective of this project was to examine P450 expression, induction, and activities in cultured human tongue cells in an attempt to provide a basic understanding of xenobiotic metabolism in this highly exposed tissue, for the purpose of contributing to the development of strategies for oral cancer prevention.; To accomplish the objective of this project, the following studies were conducted. First, initial studies were carried out to establish the presence of cytochrome P450s in the tongue, using animal models. Our animal studies revealed the existence of cytochrome P450 in the rat, rabbit, and bovine tongues as indicated by both mRNA expression and P450-dependent catalytic activities. Second, the constitutive expression of various P450 isoforms and the inducibility of oral P450s were determined using an immortalized human tongue cell line, CAL 27. The tongue cells were found to express several P450 isoforms and specific isoforms were inducible in response to both xenobiotic and endogenous liver microsomal inducers. Third, a dietary component, green tea, was included to examine its modulation effects on oral P450 isoforms. Green tea extract (GTE) was found to slightly increase the expression of selected P450 isoforms, as determined by RT-PCR and Western blot analysis. However, certain P450 activities were significantly inhibited by GTE treatment. Additionally, parallel assessment of the tongue and liver (HepG2) cells showed that the P450 expression, induction, and activities in the tongue cells were comparable to those in the liver cells.; In conclusion, our results indicate the presence of cytochrome P450s in the tongue. The data provide evidence that support the concept that several cytochrome P450s are expressed in the oral cavity and the expression can be induced. Moreover, the inhibitory effect of GTE on specific P450 activities suggests a potential defense mechanism against oral tumorigenesis. Furthermore, the similar induction pattern between the tongue and liver cells implies that the induction of specific isoforms in the tongue may occur through biochemical mechanisms that are analogous to those that are operative in the liver.