Page 181 - The Toxicology of Fishes
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Biotransformation in Fishes                                                 161


                                                                                   CYP3A56
                                                                                   Killifish
                                                                        100
                                                                                   CYP3A30
                                                                                   Killifish
                                                                  98
                                                                                   CYP3A40
                                                                                   Medaka
                                                                        77
                                                       100                         CYP3A38
                                                                                   Medaka

                                                                                   CYP3A45
                                                                                   Rainbow trout
                                                                    100
                                                                                   CYP3A27
                                                                                   Rainbow trout

                                              95                                   CYP2P3
                                                                                   Killifish
                                                                        100
                                                                                   CYP2P1
                                                                 91
                                                                                   Killifish
                                                           66                      CYP2N2
                                                                                   Killifish
                                       100                                         CYP2X1
                                                    79                             Channel catfish

                                                                                   CYP2M1
                                                                                   Rainbow trout
                                                                  68
                                                                                   CYP2K1
                                                                                   Rainbow trout

                                                                                   CYP1B1
                                                                                   Plaice

                                                                                   CYP1A3
                                                                                   Rainbow trout

                                                                                   CYP1A1
                                                                                   Rainbow trout

                       FIGURE 4.4 Phylogenic analyses of CYP in fish.

                       CYP1A—Research on CYPs in fish is more limited than that reported for mammals. Like mammals,
                       fish CYPs catalyze oxidation of many of the same endogenous substrates and environmental chemicals.
                       The most studied CYP form in fish is CYP1A. The first fish CYP1A cDNA was cloned by Heilmann
                       et al. (1988), and sequence analysis showed 57 to 59% and 51 to 53% homology to mammalian CYP1A1
                       and CYP1A2 genes, respectively. This cDNA hybridized to a 2.8-kb mRNA that was induced 10-fold
                       by 3-methylcholanthrene (3-MC) in rainbow trout. In fish, this form is generally recognized as CYP1A,
                       and the terminology is supported because mammalian 1A1 and 1A2 are believed to have diverged 250
                       MYA by a gene-duplication event (Nebert and Gonzalez, 1987), whereas fish diverged from the mam-
                       malian line prior to that time. A hybrid CYP1A gene in fish is further suggested because some regions
                       of the trout CYP1A sequence are identical to all mammalian CYP1A1 but not CYP1A2, while other
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