INTERNUCLEOSOMAL DNA FRAGMENTATION IS NOT OBLIGATORY FOR CASTRATION-INDUCED RAT VENTRAL PROSTATE CELL APOPTOSIS IN-VIVO

Castrated male rats were treated with the reversible S-1-phase cell cy cle blocking drug, mimosine, and the effects of this drug on prostate cell apoptosis was characterized, At a single dose of mimosine (25 mg/ kg/day), we found that the internucleosomal DNA fragmentation associat ed with apoptosis was partially suppressed in the rat ventral prostate at all early time points (24, 48 and 72 h) analyzed post-castration. This suppression was dose-dependent, and treatment with mimosine up to 150 mg/kg/day was sufficient to reduce the internucleosomal DNA fragm entation in the prostate by 90% at 72 h post castration. Intriguingly, this drug did not suppress the induction of mRNAs for several apoptos is-associated gene products in the ventral prostate gland (bcl-2, p53, TGF-beta and SGP-2/clusterin), Moreover, this treatment did not suppr ess the histological appearance of apoptotic bodies in the ventral pro state detectable by fast green staining of thin sections of tissue. Th e apoptotic bodies present in mimosine-treated regressing ventral pros tate tissues, however, were refractory to labeling by the in situ gap labeling method, further demonstrating lack of nuclear DNA fragmentati on in the condensed nuclei of apoptotic cells, In summary, the cell cy cle-blocking drug mimosine does not appear to affect the rate of apopt osis in the regressing rat ventral prostate gland. However, this drug was capable of suppressing the nuclear DNA fragmentation associated wi th androgen-regulated prostate cell apoptosis, These results support t he concept that nuclear DNA fragmentation is not obligatory for apopto sis, Additionally, they imply that cell cycle movement from the G(1)/S phase boundary might be important for the terminal DNA degradation as sociated with androgen-regulated prostate cell apoptosis.