Different Pathways for Mitogenic and Enzyme Induction Signal Transduction by Cytochrome P450 Inducers

E. L. Gujaeva, N. M. Ostashkina, V. F. Kondalenko, and V. A. Koblyakov^*

Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, Moscow, 115478 Russia; fax: (095) 324-1205

^* To whom correspondence should be addressed.

Received December 10, 1998; Revision received March 25, 1999

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The correlation between enzyme induction and cell proliferation caused by inducers of xenobiotic metabolizing enzymes was studied using a cell culture expressing a constitutive level of cytochrome P450 (hepatoma McA RH 7777) and a cell culture in which cytochrome P450 was absent (hepatoma 27). In hepatoma 27 cells, the inducers did not induce the synthesis of xenobiotic metabolizing enzymes but stimulated cell proliferation. Thus, the processes of signal transduction for enzyme induction and for cell proliferation by the inducers are different.

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KEY WORDS: induction, cytochrome P450, proliferation, polycyclic aromatic hydrocarbons, phorbol esters

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