Characteristics of cis-diamminedichloroplatinum-selected in vitro passaged cells derived from a transplantable rat malignant fibrous histiocytoma

A cis-diamminedichloroplatinum (CDDP)-selected cell line (MT-R10) was induced by continuous exposure of an in vitro passaged cell line (MT-P) established from a transplantable rat malignant fibrous histiocytoma (MFH-MT) to CDDP. MT-R10, capable of proliferating in the presence of 1.0 microgram CDDP/ml, was passaged in CDDP-free medium. The doubling time of MT-R10 at passage 10 (MT-R10/10) was almost the same as that of MT-P, being 22.3 and 25.5 h, respectively. The concentration of CDDP required for 50% inhibition of MT-R10/10 proliferation was two-fold higher than that of MT-P. MT-R10 consisted of round, epithelial-type cells arranged in compact sheets. Ultrastructurally, MT-R10 had numerous free ribosomes, some mitochondria, and other poorly developed cytoplasmic organelles suggesting its undifferentiated nature. MT-R10 showed no reaction for acid phosphatase or non-specific esterase. Tumors induced in syngeneic rats by inoculation with MT-R10 consisted of small, round, undifferentiated cells with scanty cytoplasm. They showed organoid and trabecular patterns, and were often arranged in compact sheets. The neoplastic cells showed no reaction for any of the histiocytic lysosomal and antigenic markers tested, but exhibited a strong reaction for alkaline phosphatase. Bone formation was often observed in the tumors. These observations suggest that CDDP-selected, undifferentiated cells may have osteogenic potential and may be one of the progenitor cells of MFH-MT.