A COMPARATIVE STUDY OF INDUCTION REGULATION IN CYTOCHROMES FAMILY 1 P450 IN CELL CULTURES AT DIFFERENT STAGES OF
TUMOR TRANSFORMATION
V. A. Evteev, N. P. Cherback, V. A. Kobliakov
Institute of Carcinogenesis, N. N. Blokhin Russian Cancer Research Centre RAMS, Moscow;
e-mail: kobliakov@rambler.ru
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.
Key words: cytochrome P450, transformation, immortalization, gene induction, benzo/a/anthracene
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