Effect of cordycepin on induction of tyrosine aminotransferase employing hepatoma cells in tissue culture

Abstract

Cordycepin acts like actinomycin in that it prevents the induction of tyrosine aminotransferase (TAT) by cortisol in the H-35 or HTC cells when added 1 2 h before cortisol. Unlike actinomycin, cordycepin did not further increase the levels of TAT which had been induced by cortisol in either the H-35 or HTC cells. Also in contrast to actinomycin, cordycepin did not interfere with the decline in TAT following removal of cortisol from the H-35 or HTC cells which had been induced with cortisol overnight. The effect of cordycepin on TAT was not a result of an effect at the translational level. Moreover when actinomycin D and cordycepin were added to the same plates the level of TAT increased thus indicating that cordycepin did not interfere with the action of actinomycin D. Cordycepin, like actinomycin D, did not block the induction of TAT by insulin in the H-35 or HTC cells, nor did it block the induction of TAT by DBC in the H-35 cells. The H-35 cells have about ten times more TAT activity than have HTC cells when both are induced with cortisol, and both lines can be induced to proportionately higher levels of activity by insulin in the presence of cortisol. Both lines respond similarly to cordycepin and to actinomycin D. Since both compounds inhibit RNA synthesis, while high levels of actinomycin D produce ‘superinduction’ of TAT with or without the presence of cordycepin it is difficult to see how actinomycin can produce this phenomenon purely in terms of the inhibition of RNA synthesis, as the Tomkins model proposes, without several additional ad hoc hypotheses.