[A comparative study of induction regulation in cytochromes family 1 P450 in cell cultures at different stages of tumor transformation].
Lipophilic xenobiotics, including some carcinogenic agents and cytostatics, are metabolized by cytochrome P450 isoforms (CYP). In tumours expression of CYP genes and their inducibility are lower than in a homologous normal tissue. This phenomenon determines the known higher cytostatic stability of tumour cells. To clarify, at which particular stage of tumour transformation the level of family 1 CYP may change, we compared mRNA expression of CYP1A1, CYP1B1 and also of proteins regulated CYP expression: Ah receptor, ARNT and AHRR. For this aim we studied embryonic and fibroblast-like cells, in addition to cells of the same types but immortalized by the Rausher virus, or spontaneously after crisis. Besides, we investigated transformed clones obtained by means of benzo/a/pyrene action on Rausher virus-immortalized cells. Constitutive expression of genes studied in all cell cultures was shown. Benzo/a/anthracene induction increases the mRNA expression of all inducible genes (CYP1A1, CYP1B1, AHRR) in the original embryonic cells, in Rausher virus-immortalized cells, and in transformed clone K2. In both spontaneously immortalized cells and transformed clone K1 only CYP1B1 was induced. In transformed clone K8 no inducible gene was induced. In summary, we have shown that: (1) the ability of immortalized cells to CYP induction is determined not only by their capacity for a non-limited persistence, but also by the nature of immortalization; (2) despite their common genesis, the transformed clones differ in their ability to induce CYP. In addition to Ah receptor and ARNT, some other, yet unknown factors may also take part in CYP induction.
Evteev
V A
VA
Shcherbak
N P
NP
Kobliakov
V A
VA
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D002461:Cell Line, Transformed; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D017931:DNA Primers; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured
D001189:Aryl Hydrocarbon Hydroxylases; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D001551:Benz(a)Anthracenes; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System; D017931:DNA Primers; D007527:Isoenzymes; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C497398:ARNT protein, rat; C492161:Ahrr protein, rat; C585499:Cyp1b1 protein, rat