@entity5 promoter-induced refractory state against XXXX decarboxylase induction by @entity864 in @entity19 epidermis.

@entity5 @entity19 @entity1880 @entity7222 @entity40065 @entity865 @entity18878 @entity864 @entity4996 @entity1968
More than one application of the potent @entity5 -promoting agent, @entity864 ( @entity865 ), to @entity19 skin at intervals of more than 48 h led to a larger induction of @entity7222 decarboxylase (EC 4.1.1.17; ODC) than did a single application. In contrast, at intervals of less than 24 h, the first application of @entity865 appeared to induce a refractory state; the second application of @entity865 did not induce ODC. The extent of the inhibitory effect caused by the first application of @entity865 was dependent on the dose. The abilities of a series of @entity4996 to induce the refractory state correlated with their promoting abilities. However, both @entity18878 and @entity40065 , potent hyperplastic agents with little or no promoting properties, induced the refractory state. On the other hand, pretreatment with @entity865 caused a refractory effect on ODC induction by mezerein but potentiated ODC induction by @entity40065 . The epidermal cells escaped from the refractory state by repeated application of @entity865 at intervals of 24 h as well as at intervals of twice a week; that is, there was a full induction of ODC activity following a second application within 24 h of a prior application. @entity865 did not elicit production of detectable ODC-antizyme activity in @entity19 epidermis. Mixing of a soluble extract from @entity19 epidermis in the refractory state with that from @entity865 -stimulated epidermis gave essentially additive ODC activity. Elimination of ODC induction by topical application of @entity1968 or injection of @entity1880 concurrent with the first application of @entity865 did not restore the ability of a second application of @entity865 to induce ODC. These results suggest that the refractory effect on ODC induction by @entity865 does not result from feedback regulation of ODC.
