[Studies on combined effect of hyperthermia and MTX to choriocarcinoma cell line (BeWo)]

Changes in cell growth and hormone production of the choriocarcinoma cell line BeWo were studied to determine the manner in which the change in the cell cycle due to antimetabolite MTX affects heat sensitivity. First of all, BeWo was treated with 10(-7)M-MTX for 48 hrs. on day 4. And heat (43 degrees C for 1 h.) was applied at various stages after MTX removal on day 6. At the same time, the change in the cell cycle induced by MTX was studied by autoradiography. The labeling index (L.I.), which was increasing until 90% by MTX exposure, still remained more than 80% up to 5 hrs. after MTX removal and then decreased to about 43% at 9 hrs. after MTX removal. The greatest effect on cell growth and HCG production was seen when heat was applied within 5 hrs. after MTX removal. And these 5 hrs. corresponded to the time when the L.I. was as high as 80 to 90%. When heat was applied more than 6 hrs. after MTX removal, the heat sensitivity was reduced in proportion to the degree of decrease in the L.I. These findings suggest that the change in the cell cycle induced by MTX has the greatest effect on the heat sensitivity of BeWo. It is therefore possible to conclude that synchronization of BeWo with S phase by using MTX or possibly other antimetabolites is very important in the application of hyperthermia.