Adaptation versus selection as the mechanism responsible for the relapse of @entity263 to XXXX ablation therapy as studied in the Dunning R-3327-H adenocarcinoma.

@entity35 @entity342 @entity263 @entity5
The Dunning R-3327-H @entity35 @entity263 is a well-differentiated, slow-growing, serially transplantable @entity5 of spontaneous origin. When intact male @entity35 bearing such an exponentially growing @entity5 s.c. are castrated, @entity5 growth abruptly stops, demonstrating the initial @entity342 sensitivity of this @entity5 . Eventually, however, after an extended period, the @entity5 invariably relapses and once again appears to grow exponentially. At the time of relapse, the @entity5 is no longer @entity342 sensitive but has irreversibly progressed to a completely insensitive state. The mechanism responsible for this irreversible progression has been demonstrated by fluctuation analysis not to be due to environmentally induced adaptation of initially @entity342 -dependent @entity5 cells to a new @entity342 -independent state. Instead, the progression is due to the basic heterogeneity of the original @entity5 (i.e., it is composed of a mixture of preexisting clones of both @entity342 -dependent and @entity342 -independent @entity5 cells). Following castration, only the preexisting clones of @entity342 -independent @entity5 cells are able to continue exponential growth; the @entity342 -dependent @entity5 cells stop proliferating and die. Thus, @entity342 ablation creates a host environment in which the @entity342 -independent @entity5 cells have a highly selective growth advantage over the @entity342 -dependent cells. Eventually, with time, this selective growth advantage results in a @entity5 which is completely composed of @entity342 -independent cells. It is the continuous proliferative growth of these @entity342 -independent @entity5 cells which leads to the relapse phenomenon.
