ABERRANT CYP1A1 INDUCTION - DISCREPANCY OF CYP1A1 MESSENGER-RNA AND ARYL-HYDROCARBON HYDROXYLASE-ACTIVITY IN MUTANT-CELLS OF MOUSE HEPATOMA LINE, HEPA-1

作者：KIKUCHI H^*; USUDA M; SAGAMI I; IKAWA S; WATANABE M

来源：Japanese Journal of Cancer Research, 1994, 85(7): 710-717.

• CYTOCHROME P-450IA1
• BENZO[A]PYRENE
• MOUSE HEPATOMA
• AH RECEPTOR

We have isolated new benzo[a]pyrene-resistant clones, cl-21 and cl-32, of the mouse hepatoma line, Hepa-l. CYP1A1-dependent aryl hydrocarbon hydroxylase activity is not inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3-methylcholanthrene in these two cell lines. However, mRNA of CYP1A1 is inducible in cl-21 and cl-32 cells, as in the wild-type cells, in spite of an undetectable level of cytosolic Ah receptor. The cl-21 cDNA of Cyp1a-1 was found to have a single mutation leading to an amino acid substitution from Leu (118) to Arg (118). However, the CYP1A1 protein band was not detected on Western immunoblots. The cDNA of cl-32 was found to have a single mutation leading to an amino acid change from Arg (359) to Trp (359). The presence of the mature protein in cl-32 was confirmed by Western blot analysis. Somatic cell hybridization experiments demonstrated that the phenotype of cl-21 and cl-32 is recessive and that these clones belong to the same complementation group. These data suggest that there may be a non-Ah receptor-mediated mechanism of CYP1A1 induction.

• 出版日期1994-7