Etoposide is widely used in the treatment of patients with
testicular cancer. The mechanism underlying apoptosis induction in
cancer cells has been studied in different cell types, but it is not known whether the same factors participate in viable germ cells undergoing programmed cell death. Since
testicular cancer primarily affects young males, we used pubertal rats (21 days old) as a model to determine different apoptotic parameters after
etoposide treatment in healthy testes. We found that one intratesticular injection of
etoposide (1.2 microg/testis) induced a significant increase in spermatocytes undergoing apoptosis, along with activation of
caspase-9, -8 and -3 after 24 h of treatment. Spermatocyte apoptosis was inhibited when a general
caspase inhibitor was added along with
etoposide.
Etoposide induces a significant stabilization/activation of p53, resulting in an increase level of this
protein. The
mRNA of Bcl-2 antagonist of cell death (BAD), a pro-apoptotic gene and a transcriptional target of p53, was significantly increased after
etoposide treatment. Thus, our results suggest a single injection of
etoposide induces apoptosis in healthy pachytene spermatocytes mediated by p53 and
caspase activation. These findings will assist the search for new
therapies to prevent the deleterious effect of
cancer drugs upon normal cells.