It has been reported that flow cytometric analysis offers good indicators to select drugs for chemotherapy of malignant neoplasms, however, there are still few reports to try to apply these data to clinical treatment. For this purpose perturbation of cell cycle traverse which induced by several anticancer drugs was studied to determined the fundamental factors to indicate the sensitivity of each drugs. Results were: 1) Drugs showed high efficiency of accumulation of cells in SG2M phase even in low concentration; MMC, AD, CQ. 2) Drugs showed high efficiency of accumulation of cells in SG2M from low concentration high concentration; Vincristine. 3) Drugs which showed accumulation of SG2M in high concentration; ACNU, BCNU. 9L rat glioma cells treated with BCNU showed high efficiency of accumulation of cells in SG2M phase. In this cell line cytocidal effect was high. However, C6 cells which showed low accumulation in SG2M even by treatment with high concentration of BCNU revealed quite resistant to anticancer drugs from nitrosourea derivatives (ACNU, BCNU). Cytocidal effect of MMC and ACNU on C6 glioma cells was studied by colony forming efficiency assay using multicell spheroids treated with these drugs and it was discussed the correlation between percent of accumulated cells and cytocidal effect of each drug.

Effect of various anticancer drugs on in vitro survival of gynecologic tumor cells were investigated by using established cell lines derived from human ovarian adenocarcinoma (HOC-21), endometrial adenocarcinoma (HEC-1B), and cervical squamous cell carcinoma (SKG-1). As compared with other established cell lines, 1) HOC-21 cells were more sensitive to Cis-platinum, Adriamycin, and actinomycin-D. 2) HEC-1B cells were more sensitive to progesterone. 3) SKG-1 cells were more sensitive to bleomycin and mitomycin-C. These results are consistent with the clinical effects of various anticancer drugs, and established cell lines derived from various human gynecologic tumors are useful to select effective anticancer drugs in vitro.

Effect of M3, an anticancer agent, on the phagocytic activity of the mouse reticuloendothelial system was studied by the carbon clearance method. Lysosomal enzyme activities of peritoneal exudate cells solution (PECs) and peritoneal macrophage (Mp), and morphological changes of Mp were also examined. The K index (phagocytic index) was significantly increased 24 hr after the administration of M3 (250,300 mg/kg, i.p. X 3) as well as that of zymosan (Z: 50 mg/kg, i.p. X 3). The time course on phagocytic activity of Me (300 mg/kg) was also investigated. The index was increased 2, 4, and 96 hr after i.p. administration, but on i.v. administration the index was decreased at 2 and 4 hr, although increased at 72 hr. Microscopically, carbon particles were internalized by Mp of marginal zones between white and red pulp in the spleen, and in the liver, mainly by Kupffer cells. Lysosomal enzyme activities (acid phosphatase and beta-glucuronidase) and cell numbers of PECs were increased as follows: Z greater than M3 greater than Na2HPO4. These enzyme activities in Mp were also increased significantly 72 and 96 hr after i.p. administration. Observing of morphology by Giemsa staining, saline and Na2HPO4 groups showed round monocytes, but in the M3 and Z groups there were enlarged cells with many projections. These results suggest that M3 promotes the phagocytic activity on the reticuloendothelial system in mice and has a stimulatory effect on Mp because of the increase in the lysosomal enzyme activities and morphological changes in the cells.

Enhancement of antitumor transplantation immunity was observed in rats by treatment with the antileukemia drug busulfan (BU) both 5 days before and 5 days after immunization with X-irradiated tumor cells. The mechanism of the enhancement induced by BU may be due to a selective elimination of the suppressor cells from the immunized host. Similar enhancement of immunity was also observed by using other anticancer drugs when only cyclophosphamide (40 mg/kg) was given before the immunization and futraful (300 mg/kg) and mitomycin c (1 mg/kg) were given offer the immunization. However, adriamycin (4 mg/kg) did not show any enhancing effects on immunity either before or after the immunization.

Aclacinomycin A, a new anthracycline antitumor antibiotic, was given to rabbits by single instillation or single intracutaneous injection and to guinea pigs by single subcutaneous or intramuscular injection to examine the irritative effect. Slight dilatation of blood vessel and swelling in the conjunctiva and nictitating membrane were observed in the eyes of rabbits given 1% solution. Edema in the bulbar conjunctiva, iris and cornea was histologically noted. Washing of the eyes after drug instillation prevented these damages. Subcutaneous and intracutaneous injections of 1% solution (0.2 ml) gave hyperemia, swelling and necrosis at injection site. Cellular infiltration, fibrosis and necrosis were histologically detected. Intramuscular injection of 1% solution (0.2 ml) also provided induration and swelling at injection site. Histologically cellular infiltration and necrosis were observed. These irritative effects were much slighter in administration of 0.1% solution. No change was observed with 0.01% solution.

Japan White rabbits were treated with aclacinomycin A, a new anthracycline antitumor antibiotic, at a dose of 6.25 or 25.0 mg/kg by single intravenous, or 12.5 or 50.0 mg/kg by single oral administration, respectively. Beagle dogs were treated at a dose of 3.0 or 6.0 mg/kg by single intravenous injection. In rabbits in higher dose groups, RBC and WBC counts as well as lymphocyte ratio in peripheral blood decreased on day 1. Nucleated cell counts and erythroid elements in bone marrow decreased to raise M/E ratio (Myeloid/Erythroid ratio) on day 3. In a dog given at 6.0 mg/kg, WBC and platelet counts, lymphocyte and neutrocyte per cents in peripheral blood and also nucleated cells, particularly erythroid elements in bone marrow remarkably decreased on day 3 accompanied with an increase in M/E ratio. These changes were almost completely recovered by day 14 in both animals. No abnormalities were found in lower dose groups. Male Wistar rats, treated with the drug at a dose of 1.5 mg/kg by daily intraperitoneal injection for 30 days, showed slight decreases in peripheral WBC and RBC counts and M/E ratio in bone marrow. No change was observed in rats treated at 0.75 mg/kg and less for 30 days.