Reversal of Cytochrome P-4501A1 and P-450-EF Expression in MCA-C3H/10T1/2 Cell-derived Tumors as Compared to Cultured Cells

摘要: The 3-methylcholanthrene-transformed tumorigenic cell line, MCA-C3H/10T1/2 CL15 (MCA), expresses the novel benz( a )anthracene (BA)-inducible polycyclic aromatic hydrocarbon-metabolizing cytochrome P-450 (P-450-EF). level of expression is comparable to that reported for nontumorigenic C3H/10T1/2 CL8 (10T1/2) cells (Pottenger, L. H., Christou, M., and Jefcoate, C. R. Arch. Biochem. Biophys., 286: 488–497, 1991). Sarcomas (3–12 mm in diameter) generated athymic “nude” mice by s.c. injection MCA exhibited much lower 7,12-dimethylbenz-( )anthracene-metabolizing activites (5–15% levels cultured cells), both constitutively after vivo treatment with BA. A sharp decrease P-450-EF was observed at functional (10- 30-fold) (as determined antibody inhibition studies) apoprotein (50- > 100-fold) Western immunoblots). However, contrast BA-treated which comprises essentially total spectrally detectable content (∼30 pmol/mg) virtually undetectable P-4501A1, tumors from these expressed substantial P-4501A1 immunodetectable protein response BA (∼0.5–3 pmol/mg). In tumors, decreased or barely detectble ( 95%) as apoprotein. contribution consistent full hemoprotein. Tumor size affected dimethylbenz( )-anthracene-metabolizing activities/mg microsomal (small were 2- 3-fold more active than large tumors) but had no effect on ratio dependent on, respectively, holoenzymes (1.5:1), thus suggesting controlled coexpression proteins. Reculturing tumor-derived effected partial restoration eliminated confirming unique tumor environment regulation genes. Possible mechanisms an environment-dependent concerted genes are discussed.