JBC, Vol. 250, Issue 19, 7766-7770, Oct, 1975
Regulation of aryl hydrocarbon (benzo-(A)-pyrene) hydroxylase activity in mammalian cells. Induction of hydroxylase activity by N6,O2'-dibutyryl8 adenosine 3':5'-monophosphate and aminophylline
H. Yamasaki, E. Huberman and L. Sachs
Treatment of hamster BHK cells with N6,O2'-dibutyryl adenosine
3':5'-monophosphate (Bt2cAMP), aminophylline, theophylline, or papaverine
increased the level of aryl hydrocarbon (benzo(a)pyrene) hydrolxylase
activity. The highese increase, 100-fold, was obtained with Bt2cAMP plus
aminophylline or theophylline. N2,O2-Dibutyryl guanosine
3':5'-monophosphate gave a lower induction than Bt2cAMP. The level of
hydroxylase activity started to decrease 6 hours after treatment with the
inducer and was reduced to almost the uninduced level after 24 hours.
Repeated addition of Bt2cAMP and aminophylline did not prevent this
decrease. The hydroxylase can also be induced by treating cells with
benz(a)anthracene, and the level of this induced activity was maintained
for 24 hours. Aminophylline gave a 2- to 8-fold stimulation of the
induction by benz(a)anthracene. The enzyme activity induced by Bt2cAMP,
aminophylline, and benz(a)anthracene converted benzo(a)pyrene to similar
alkali-extractable metabolities with a fluorescence spectra similar to that
of 3-hydroxybenzo(a)pyrene. These induced enzyme activities also showed a
similar heat stability. Induction by Bt2cAMP and aminophylline, like
induction by benz(a)anthracene, required continued protein synthesis and
only an initial period of RNA synthesis. Compared to the
benz(a)anthracene-induced hydroxylase with a Km of 4.3 muM, the hydroxylase
induced by Bt2cAMP and aminophylline showed a Km of 0.14 muM, and was
100-fold more sensitive to inhibition by 7,8-benzoflavone. Increasing the
serum concentration in the culture medium stimulated the induction by
aminophylline but did not stimulate induction by benz(a)anthracene. The
results indicate that aryl hydrocaarbon (benzo(a)pyrene) hydroxylase can be
induced by compounds that increase the level of adenosine
3':5'-monophosphate and that this induction and induced enzyme activity
differs from that caused by benz(a)anthracene.
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