[Study on so called "cellular effect" of methotrexate on choriocarcinoma and its mode of manifestation (author's...

The "cellular effect" i.e. temporary elevation of HCG titer may not be infrequently experienced during course of chemotherapy against choriocarcinoma. Present paper is to clarify real view of the effect and mechanism of its manifestation by using a cell-line (GCH-nu). 1) Cellular growth was suppressed moderately by 10(-7), 10(-6) and 10(-5)M MTX. 2) During 2-4 days of administration at these concentrations of MTX HCG per ml medium was elevated 5 times. HCG in cells per mg protein were also higher 5-7 times. 3) HCG-beta in media was enhanced 5-7 times in MTX group. 4) Estrone, estradiol and progesterone were not altered. 5) Choriocarcinoma cells developed marked enlargement of nuclei and cells, multinucleation and cytoplasmic vacuolization. 6) Cytochemistry of heat stable ALP revealed increased activity especially in cells with morphological changes. ALP examined by biochemical method was enhanced 5 times. 7) Amount of protein per cell increased 10 times after giving MTX. Real view of so-called "cellular effect" includes elevations of HCG-beta and ALP activity as well as HCG, whereas sex steroids are not apparently related. The data in addition to morphological and cytochemical changes reveal that MTX may induce differentiation of choriocarcinoma cells into those of syncytial type, which then sustain the "cellular effect".