In order to search for new compounds with higher anti-cancer activities and lower toxicities, 18 dehydrogenated carboncyclic analogs of norcantharidin, of which 17 are unknown compounds, were designed and synthesized. Preliminary screening results revealed that compound V6, VI1 and VI4 exhibited fairly apparent inhibitory activity against the growth of human-hepatoma cells, Bel-7402, in vitro. The inhibitory rate of VI4 is 52%, almost the same as that of norcantharidin, in the concentration of 0.05 mumol/ml.

Twenty three 4-(2-amido-2-ethoxycarbonyl) ethylsulfenyl-4-deoxy-4'-demethylepipodophyllotoxin analogues were synthesized by three steps, in which trifluoroacetic acid was used as a condensation agent of 4'-demethylepipodophyllotoxin with L-cysteine ethyl ester hydrochloride without any protection of phenolic hydroxy and amino groups. All compounds were screened in vitro against L1210 leukemia and KB cells, in which, compounds 11, 16 and 18 exhibited more potent antitumor activity than etoposide.

In order to search for new compounds with higher anti-cancer activities and lower toxicities, 19 amino acid derivatives of norcantharidin, of which 16 are unknown compounds, were designed and synthesized. Preliminary screening results revealed that 2-(syn-exo-7-oxabicyclo [2.2.1] heptane-2,3-dicarboxylic imido)-N-phenyl glutaramic acid exhibited a fairly apparent inhibitory activity against human-hepatoma cells in vitro (inhibitory rate 39.4% at 0.025 mumol/ml).

Glyciphosphoramide (GPA) is one of the anticancer agents belonging to the group of phosphoramide mustard. It has apparent antitumor effects in some animal models and in clinical trials against breast cancer, lymphosarcoma, uterocervical cancer and cancerous ulcer with good results. In this paper, the determination procedure of GPA and its metabolite using nitrobenzylpyridine (NBP) method is reported. The absorbance of the coloured products from the reaction of hydrolyzed or metabolized GPA with NBP was measured at 570 nm and 564 nm, respectively. The linearity of the reaction for GPA and its metabolite was established over the range of 6.25-100 micrograms/ml water or plasma. The plasma of rats and mice was found to be able to metabolize GPA to form alkylating agent (s) which react with NBP, but that of rabbits cannot. The plasma concentration-time curve of metabolite obtained after oral administration of GPA (100 mg/kg) in rats was shown to fit a two compartment open model with the following parameters: T1/2 beta = 44.5 min, T1/2 alpha = 3.16 min, T1/2 Ka = 2.14 min, T1/2Km = 0.0644 min, Tmax = 7.57 min, Cmax = 55.8 micrograms/ml, AUC = 2827. 39 micrograms/ml.min, K21 = 0.09663/min, K10 = 0.03535/min, K12 = 0.1030/min, Vc = 1.00 L/kg, Vd = 2.07 L/kg, CLt = 2.12 L/h. Kidney was found to be the main organ for GPA metabolite elimination. About one fourth of the given dose was excreted in urine within 24 h with the main portion excreted in the first 2 h.

The cytotoxicities of 2 derivatives of artemisinin B and 2 derivatives of artemisic acid (designated as Compound A, B, C, and D) were investigated, using trypan blue dye exclusion test and colony-forming units assay. At the concentration of 5 micrograms.ml-1, the inhibition rates of these 4 compounds against murine leukemia cell line P388 were > 85%. When tested against human hepatoma cell line SMMC-7721 at 25 micrograms.ml-1, the inhibition rates of Compound A, B, C, and D were found to be 92.3%, 96.9%, 84%, and 82.1%, respectively, and 27%, 8%, 37.8%, 1.7% against normal human embryonic lung cell line WI-38, respectively. These 4 compounds all showed an inhibition rate of 100% against human gastric cancer cell line SGC-7901 at 50 micrograms.ml-1.

Natural non-antibiotic producing Streptomyces sp. 1254 was mutagenized by UV irradiation and two active mutants were isolated. Mutant 113 produced novel anthracycline compounds designated mutactimycins. Mutactimycin A was active against the bacteriophage of Bac. subtilis and some viruses in tissue culture. The mutant 2-6 synthesized a basic water-soluble antimicrobial antibiotic. Chemical analysis of the whole cell hydrolysate and the morphological characterization showed that the strain 1254 and its mutant 2-6 were of chemotype I, belonging to the genus of Streptomyces, and the mutant 113 was of chemotype IV without mycolic acid. Co-synthesis test of strain 1254 and a blocked mutant of strain 113 gave the active compounds identical with mutactimycins. Using the actI gene as a probe, the Southern hybridization revealed homology between the actinorhodin polyketide biosynthase gene and the total DNA of the strain 1254. Based on these data it was deduced that Streptomyces sp. 1254 should have a biosynthesis pathway for mutactimycin, but some of its genes might fail in expression and mutagenesis would make the silent gene(s) active.

Result of animal experiment proved that Yi Kang Ling, a TCM compound preparation, could markedly inhibit the growth of implanted tumour in mice. The inhibiting effect to the experimental tumour of combined therapy of Yi Kang Ling and the chemotherapeutic agents-CTX or MMC was better than that using singly. The Yi Kang Ling could alleviate toxicity of chemotherapy which caused the weight loss of mice. It could markedly increase the immune organs' weight, raise the phagocytosis of abdominal macrophage and promote the formation of serum hemolysin inhibited by CTX. The experimental result revealed that the combined therapy of Yi Kang Ling and the chemotherapeutical agents could enhance anti-tumour effect and lower the toxicity of chemotherapy. Toxicological experiment showed that the Yi Kang Ling did not have any toxic effect against organism.

Human promyelocytic leukemia HL-60 cells provide a useful model system for the study of cell differentiation in vitro. Here the growth of HL-60 cells as a solid clot with fibrin in subrenal capsules (SRC) of mice was studied. The cell volume of HL-60 cells increased 5 and 15-fold between 6-9 days after transplantation into normal and CYT immunosuppressed mice, respectively. Histological study revealed typical proliferation and invasion characteristics of HL-60 cells and higher tumor cell density. RA, RII, Ara-C, Harringtonine and HMBA significantly inhibited the growth of HL-60 cells in SRC of mice. This model provides a useful system for the study of the effect of drugs on cultured tumor cells or leukemia cell lines in vivo.

According to the principles of SOS response, the authors tested the mutational specificity of tea and its inhibitory effects to the mutational specificity of 6 antineoplastic drugs by using the method of mutational and anti-mutational synchronous test. The results revealed that the tea had no mutational toxicity but anti-mutation effect. It also had the inhibitory effect on mutational toxicity of 6 antineoplastic drugs, including Mitomycin C, Bleomycin, Fluorouracil, Cisdiaminodichoroplatinum, Arabinosylcytosin and Mustargen. These results have provided referential basis for further study on anti-cancer effect and clinical use of tea.

To investigate the effects of combination chemotherapy on ovarian cancer in vitro, we observed the sensitivity of tumors to different drugs by incorporation assay of tritium thymidine (3H-TdR). The results revealed that the drugs and their sensitive degrees varied from tumor to tumor. Whether the combination of the drugs is synergism or sometimes only enhances toxicity depends on the difference of individuals. We suggest that in vitro anti-cancer drug sensitivity test could be applied in selection or determination of chemotherapy protocol.

The effect of harringtonine (Har) alone and in combination with verapamil (Ver) on the proliferation of human leukemia-60 (HL-60) cells in vitro were studied. IC50 of Har alone to the cells was about 49 ng.ml-1 which was reduced to its 1/3.3 and 1/4.5 when used with Ver 1 and 2 micrograms.ml-1, respectively. In colony forming test, the survival fraction of the HL-60 cells treated with Har 15 and 30 ng.ml-1 plus Ver 2 micrograms.ml-1 was reduced to 1/3.3 and 1/8 of the cells as when treated with Har alone, respectively. The results suggested that Ver enhanced the antitumor activity of Har in vitro and may used as an enhancer of Har in vivo.

To assess the usefulness and the sensitivity of the nuclear anomaly test in human lymphocytes we treated in vitro human whole blood with various concentrations of mitomycin C, thiotepa, and bimolane. After the blood samples had been stored at 37 degrees C for 17-18 h, smears of isolated lymphocytes were made. The nuclear anomalies (micronuclei, irregular, karyorrhectic, and pyknotic nuclei) were measured. The concentration-response relationship and the minimum sensitive concentration of nuclear damage indices to the test mutagens were analyzed. The results showed that all 3 drugs induced a concentration-dependent increase of other nuclear anomalies except pyknotic nucleus in lymphocytes, that the most sensitive index of nuclear damage was the micronucleus assay, that the karyorrhectic assay was as sensitive to MMC and bimolane as the micronucleus assay, and that the irregular nucleus assay and the complex nuclear anomaly assay were less sensitive, but the correlation between concentration and complex nuclear anomalies was the best among various indices of nuclear damage. Therefore, the in vitro nuclear anomaly test in lymphocytes of human whole blood could be used to evaluate genotoxic effects of chemicals.

The inhibitory effects on the mutational specificity of antineoplastic drugs of 14 kinds of vitamin were tested with the method of mutational and anti-mutational synchoronous test, add S9 and no S9. Vit C, Vit B6, and nicotinic acid had distinct inhibitory effects on the mutational specificity of 6 antineoplastic drugs, namely, mitomycin C, bleomycin, fluorouracil, cis-Diaminodichloroplatinum, arabinosylcytosine and mustargen Vit K3 showed inhibitory effect to mitomycin C, fluorouracil, cis-diaminodichloroplatinum, and arabinosylcytosine but Vit AD, Vit B1, Vit B2, Vit Bco, Vit D3, Vit E, Rutin, Vit K1, Vit K4 and folic acid did not. The fact that Vit C, Vit B6, nicotinic acid and Vit K3 showed anti-mutational effects is of some significance with reference to clinical therapeutics and prevention of tumours.

The antitumor activity of GP-7, a new spin-labeled epipodophyllotoxin, was studied by liquid scintillation spectrometry. There were many similarities between GP-7 and etoposide. Both GP-7 and etoposide inhibited the incorporation of [3H]TdR, [3H]UR, and [3H]Leu into DNA, RNA, and protein synthesis in leukemia 7712 cells. The inhibition correlated with drug concentration and duration. IC50 of GP-7 and etoposide on DNA synthesis at 24 h were 0.21 and 0.37 micrograms.ml-1, respectively. The inhibition of GP-7 or etoposide on DNA synthesis retained even after the drug were washed out for 3 h. GP-7 and etoposide caused DNA single-strand breaks, with a well concentration-response relationship. These data suggest that the inhibition of DNA synthesis by GP-7 or etoposide is likely due to the damage of DNA template and breaking of single-strand DNA.

Glyrrhiza Uralensis (GU) and Chelidonium Majus (CM) are two kinds of Chinese herbal medicine. GU and CM not only exert much stronger effects in blocking mutagenesis due to strains of Salmonella typhimurium (TA 97, TA 98, TA 100, TA 102), but also have different degrees of obstructing mutagenesis induced by Furapromidum (F30066), Zhengdingmycin Hydrochloride (DM), N-methyl-N1-nitro-N-nitrosoguanidine (MNNG) and Methyl-methanesulfonate (MMS). The blockage effect of GU and CM obviously depends on the doses used. GU and CM could also impede the occurrence of stomach cancer induced by MNNG, and the impeding rate is about sixty percent.

The clinical effect of the granule of Shencao Fuzheng Kangai had been proved and the animal experiment was carried out. The results showed that: (1) No toxic response was found in acute toxicity test. (2) The granule could prevent WBC from decreasing severely in chemotherapy experiment (P less than 0.01). (3) It was indicated that the granule could improve the phagocytic function of macrophage in carbon clearance experiment (P less than 0.01). (4) It was meant that the granule could inhibit the growing of some solid carcinoma in inoculation experiments.