To study the effects of etoposide on experimental testicular teratoma in 12
9/SvJ mouse we analysed the tumour growth, differentiation, apoptosis and t
he localisation of mdr, P-glycoprotein (mdr(1)-Pgp). In this model the impl
anted gonadal ridges developed into testicular teratomas in 17 out of 56 im
planted testes (30%) and in 14 out of 28 mice (50%). The tumour-bearing mic
e were treated with etoposide on 4 successive days either 4 weeks or 6 week
s after implantation, and killed 7 days after the last dose. The mice in th
e control groups did not receive etoposide. The teratomas consisted mainly
of neural tissue. The etoposide-treated 4-week teratomas, but not the 6-wee
k teratomas, were significantly smaller than those in the corresponding con
trol groups. The density of apoptotic cells and the distribution of the mdr
(1)-Pgp were not altered by etoposide. The decreased proportion of immature
neuroectodermal tissue components was observed in all treated teratomas, c
onverting the histology towards that of a mature teratoma. In addition, a l
ow proportion of immature tissue components was frequently combined with a
low density of apoptotic cells. In conclusion, etoposide decreased the imma
ture tissue components of teratomas, while mature tissues remained unaffect
ed. These results may have clinical relevance in man, since they confirm th
at postchemotherapy mature teratomas cannot be treated with chemotherapy. D
espite benign histology, the human residual tumours have a significant mali
gnant potential and require complete surgical excision and close surveillan
ce.