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.

A new component of antitumor action TG has been isolated from the ethyl acetate extract of Tripterygium wilfordii (besides Triptolide, Tripdiolide and Triptonide). TG was shown in this study to have obvious antitumor effects. The average life span of H22, S180, EAC and breast carcinoma-bearing mice treated with TG ip x 2 days were 100% more than those of the control mice (P less than 0.01) TG was able to inhibit tumor growth of S37-bearing mice at the dose of 150 mg/kg per day, ig x 3, its inhibitory rate was 42% (P less than 0.01). TG could also inhibit squamous epithelial lung carcinoma induced by 3-methylcholanthrene. The inhibitory rate was 65.13% (P less than 0.05). TG had remarkable killing effect on human HL60 and Daudi cells and two direction effects on function M phi of mouse abdominal cavity in vitro.

Using mutational and anti-mutational synchronous in SOS inductest (+/- S9), We found that 7 out of 11 kinds of commonly eaten vegetables had the ability to inhibit mutagenicity caused by chemical drugs such as Mitomycin C, Bleomycinia, Fluorouracil, Cis-Diaminodichloroplatinum, Arabinosylcytosin and mustargen, They were garlic, green Chinese onion, onion, garlic bulb, tomato, cucumber and water radish. The other 4 lacking this ability were rape, chinese toon, ginger and asparagus lettuce stalk. We believe that our results can be helpful in the preparation. of cancer patients' diet, who are receiving chemotherapy and in the prevention of cancer.

Chemosensitivity testing of adenocystic, tongue and gingiva cancer cell lines to 14 antitumor drugs using a tetrazolium-based colorimetric assay (MTT assay) was carried out and the values of the relative antitumor activity (RAA) of the drugs were compared. Adriamycin (ADM), methotrexate (MTX) and fluorouracil (5-FU) showed the most potent RAA against the cell lines while Cantharidin (CTD) did not show RAA. The rank orders of other 10 drugs against each cell line differed from each another.

Two new compounds hancogenin B (V) and hancoside A (VI) and four known compounds glucogenin C (I), cynatratoside A (II), glaucogenin A (III) and anhydrohirundigenin (IV) were isolated from the roots of Cynanchum hancockianum (Maxim) Al. Iljinski. Their structures were identified on the basis of spectral evidence. The fragmentation ways of 13:14, 14:15-secopregnenes in EIMS were outlined and the antitumor activity of II and the antiendotoxic activity of VI were also preliminarily tested in vitro.

C1027, a new macromolecular peptide antitumor antibiotic produced by Streptomyces globisporus C1027, shows extremely potent cytotoxicity to cultured cancer cells. The antibiotic is composed of an apoprotein and a chromophore and the latter serves as the active part of the compound. C1027 was separated into apoprotein and chromophore by methanol extraction and the separated parts can be reconstituted to form the active C1027 molecule in phosphate buffer. For determination of the specificity of C1027 reconstitution, the apoprotein was incubated with epirubicin and the chromophore was incubated with H16, a McAb directed against hepatoma cells. Notably, the reconstitution of C1027 occurred neither between apoprotein and epirubicin nor between chromophore and IgG molecule. In addition, bovine serum albumin showed no competition with C1027 apoprotein in binding to the chromophore. Various methods for linking C1027 to McAb were studied and two kinds of immunoconjugates have been prepared: (1) direct conjugate was made by linking C1027 to McAb, using SPDP as a linker agent, (2) assembled conjugate was made by linking and reconstitution, including 3 steps. Firstly, the chromophore was extracted with methanol and stored at -70 degrees C in drak. Secondly, the apoprotein was conjugated to McAb by SPDP and finally the extracted chromophore was added to the McAb-apoprotein conjugate. Determined by clonogenic assay, the IC50 values for hepatoma cells were 42 pmol/L, and 5.5 pmol/L, respectively, for direct conjugate and assembled conjugate. The IC50 value of M3-C1027 assembled conjugate prepared by linking the irrelevant McAb M3 to C1027 was 1,400 pmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteannuin B (I) was converted to hydroxy lactones (VII, VIII) by a mixture of formic acid and sulfuric acid. Compound VI and Compound VII both showed activity against leukemia P 388 cell in vitro. The rate of growth inhibition were 97.5% and 11.8% for (VI) and 80% and 52.6% for (VII) at the concentration of 10 and 1 micrograms/ml respectively. It seems that the antileukemia activity of 6-membered lactone is higher than that of 5-membered and the methylene group is necessary for the antileukemia activity.

Twelve compounds were isolated from Annona squamosa. Their structures were identified as liriodenine (AS-1), moupinamide (AS-2), -(-)-kauran-16 alpha-ol-19-oic acid (AS-3), 16 beta, 17-dihydroxy-(-)-kauran-19-oic acid (AS-4), anonaine (AS-5), 16 alpha, 17-dihydroxy-(-)-kauran-19-oic acid (AS-6), (-)-isokaur-15(16)-en-17,19-dioic acid (AS-7), squamosamide (AS-8), 16 alpha-methoxy-(-)-kauran-19-oic acid (AS-9), sachanoic acid (AS-10), (-)-kauran-19-al-17-oic acid (AS-11), daucosterol (AS-12). Among them, AS-8 is a new amide, AS-9 is a new natural product.

The biotransformation of etheofazine (EDMTP), a new anticancer drug, was studied by using isolated perfused rat liver. Two main metabolites were separated from the perfusate by HPLC and TLC and their chemical structures were determined by MS, 1H-NMR and IR. EDMTP-I is the parent compound. EDMTP-II is 7-ethyl-8-aminotheophylline. EDMTP-II was also separated and identified from the blood of mice after iv of 10 mg/kg. Species difference of biotransformation of EDMTP between rat and mouse seems to be not significant in this study.

Some beta-germanyl-alpha-amino acid derivatives were prepared from the reaction of HGeCl3 with substituted oxazolines. The compositions of the above compounds were studied using IR, element analysis and so on. Experimental results were as follows: for 1-substituted-2-amino-2-carboxyethylgermanium susquioxide (such as IIIb), the po LD50 for mice was found to be above 10 g/kg. When given ip, a maximum inhibition of 50% of the growth of S180 was obtained for IIIb, whereas an inhibition of 42% was achieved for 5-Fu under the same experimental condition.

Pseudohainanensine (HH08) is a synthetic compound which is active against L-1210. In order to study the pharmacokinetic characteristics of this compound in rats, 3', 4'-dideuteropseudohainanensine (DH08) was synthesized and used as internal standard in GC-MS determination for quantitative analysis of alkaloid HH08 in the blood of rats that had been given HH08 at a dosage of 10 mg/kg intravenously. Experiments demonstrated that the detection limit of HH08 was 3 micrograms/ml and the peak concentration in the blood was 13.1 +/- 0.2 micrograms/ml after a single intravenous injection (one min. after injection). The biological half life time can be divided into two phases; the fast phase (alpha) 2.61 min, and the slow phase (beta) 42.59 min. Two hours after the injection no drug could be detected in the blood.