Ihe effed of pretreatment of Candida plbicans rpith two antineoplasbc agents (thiotepa and methotrexate) on experimental cendidosis m mice was stndied. In vitm treatment of C.albicans with these two -toxic drags altered its pathogenicity in two Merent ways. Pretreatment with thiotepa seems to definitely enhance the pathogenicity of C. albicans as evidenced by mammpic and microscopic findings. In contrast, pretreatment with methotrexate seems to exert a beneficial effed as measured by the same &ria. Pretreatment of the host with tbiotepn gave similar enhancement as that observed with thiotepa-treated microorpnkms. However, treating the host with methotrexate gave a contrasting pidxue to that obtained by treating the yeast itself with this drag. l'hese findings snggest thrt tbiotepa enhances the pathogenicity of C. albicans in one of two ways: (1) By exertiug an effed on the yeast itself and as such, making it more invasive. (2) By exerting an effect on the host, compromising its defence system and making it more susceplible to infedion by this orgrmism. By comparison, the mechanism by which methotrexate potenliates the effects on C. albicans is through an effect on the host solely and not through the oxganim The dinical implication of these findings is discnssed. Zusammenfassnng: Znn3ichstwnrde der E M eiuer Vorbehandhmg von h d i d a albicans mit zwei Qtostatica ("Motepa und Methotrexat) a d die experimentelle Candidost? bei Miitwen mtemcht. Die Voinkubation von h d i d a nlbicans mit diesen beiden cgtotoxischen Medikamenten beeinnnste ihre Pathogeniti[t m zweiedei We&. Wie mPkroskopiscbe nnd milwskopische untersnebnngen zeigen, debt eiue Vorbehandhmg mit Wtepa eindentig die Pathogenitiit von h d i d a a l b i zll steigem. Im Gegensak dazn lie6 sich bei Vohehandlung mit Methotrexat eher em giinStiger H e k t aufzeigen. Die Vorbehandhmg des Wirtsorganismus mit 'Ihiotepa e m eine ihlicbe Steigerong der pltbogenitiit, wie sie bei der Vorbehandlnng der Hefen mit W t e p a beobachtet worden waren. Im Gegensatz dazn zeigte sich bei Vohhandlung des Wmrganismus mit Methotrexat em Kid, das von dem abwich, wie es erhalten wnrde, mykosen 28, No. 8 (1985) Antineoplastic Agents The antineoplastic agents used in this study are: Methotrexate (MET): -N-(4-[(2,4diaminopteridind-ylmethyl)-methylamino]bemyl-Lglutamic acid (Cyanamid International Corporation -Switzerland) and thiotepa (THT): N,N:N"triethylenethiophosphoramide (American Cyanamid Company N. Y). Both drugs were of pharmaceutical grade.Preparation of Znoarlum: Cells were grown at 37% in a rotary shaker in 50 ml quantities of yeast nitrogen base (Difco) supplemented with 2.5% dextrose (YNBD) and adjusted to pH 6.0. Three different batches of cells were grown: a) Celis grown in the presence of 0.0 p g d ' of drug (control) b) Cells grown in the presence of 500 pgml-' of MET c) Cells grown in the presence of 500 pgml-' of THT.Enough flasks of each category were used to give sufficient cells for injection. After 24 hours cells were harvested by centrifUgation, washed twice ...