title: In vitro kinetics of two human CYP1A1 variant enzymes suggested to be associated with interindividual differences in cancer susceptibility.
abstract: A genetic polymorphism (A4889-->G) in the human CYP1A1 gene which creates an Ile462-->Val amino acid substitution has been suggested to cause altered enzymatic properties of CYP1A1. Since several epidemiological studies have shown an association between the CYP1A1-Val allele and lung cancer, we considered it of importance to evaluate the in vitro kinetic properties of the two CYP1A1 variants after expression of each cDNA in yeast. No differences were found in K(m) or Vmax for CYP1A1 dependent O-dealkylation of ethoxyresorufin and 3-hydroxylation of benzo(a)pyrene between the two variants. The data indicate that the Ile/Val polymorphism in human CYP1A1 is not functionally important.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Persson
authors.forename: I
authors.initials: I
authors.lastname: Johansson
authors.forename: M
authors.initials: M
authors.lastname: Ingelman-Sundberg
mesh_terms: D001564:Benzo(a)pyrene / Q000378:metabolism; D003001:Cloning, Molecular; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D004198:Disease Susceptibility; D014644:Genetic Variation; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008175:Lung Neoplasms / Q000209:etiology*; D010078:Oxazines / Q000378:metabolism; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D010078:Oxazines; D011994:Recombinant Proteins; D001564:Benzo(a)pyrene; C007649:ethoxyresorufin; C014180:resorufin; D019363:Cytochrome P-450 CYP1A1