Gan最新文献

The clonal origin of radiation-induced thymic lymphoma was studied in mice with cellular mosaicism for phosphoglycerate kinase (PGK). Repeated whole-body X-irradiations (4 doses, 1.7 Gy each) with intervals of 7 days resulted in development of thymic lymphomas in the mosaic mice. PGK from all lymphomas gave only a single spot on electrophoresis. The results demonstrate the single cell origin of the thymic lymphoma.

Correlation studies between the sensitivity of tumor cells determined by clonogenic cell assay and the clinical effect of chemotherapy were performed in patients with primary lung cancer. Thirty-four of 48 patients showed adequate colony formation (greater than or equal to 30 colonies) to test in vitro chemosensitivity. Colony formation of tumor specimens did not differ with regards to prognostic factors such as sex, age, stage, performance status, and prior chemotherapy. The two criteria of in vitro chemosensitivity employed were greater than 70% and 50% reduction in colony numbers. When in vitro chemosensitivity was defined as a colony reduction of greater than 50%, the true positive rate in the assay was 57%, while the true negative rate was 85%. In this case, the predictive accuracy was 79%. When in vitro chemosensitivity was defined as a colony reduction of greater than 70%, the true positive rate for the assay was 100%, while the true negative rate was 81%. In this case, the predictive accuracy was 82%. By Fisher's exact probability test, the overall in vitro/in vivo correlation was statistically significant (P = 0.042 less than 0.05) with the 50% cut-off point, but was not significant (P = 0.053 greater than 0.05) with the 70% cut-off point.

One of the quinoline-DNA base adducts, QGI, formed in cells treated with 4-nitroquinoline 1-oxide, was readily prepared in vitro from GMP or dGMP and 4-hydroxy-aminoquinoline 1-oxide in the presence of ATP, L-serine, and seryl tRNA synthetase. Synthetic seryl-AMP could be substituted for the enzymatic activation system for QGI formation. Chemical and spectral analyses of the adduct thus prepared revealed that QGI can be formulated as N4-(guan-8-yl)-4-aminoquinoline 1-oxide, the structure of which is identical with the modified base structure involved in the deoxyguanosine-quinoline adduct, dGIII (nomenclature of Loucheux-Lefebvre et al.) obtained by the chemical modification of deoxyguanosine with monoacetyl and diacetyl derivatives of 4HAQO.

A new strain of Epstein-Barr virus was isolated from an epithelioid hybrid cell line derived from nasopharyngeal carcinoma which had been cultured for 14 days at 32 degrees. This virus can transform human cord blood lymphocytes and induce early antigens in Raji cells.

On the basis of paradoxical concanavalin A (Con A) staining, the tendency of tumor cells of gastric phenotype to shift to intestinal phenotype and the stability of the latter phenotype in stomach tumors of different sizes were examined quantitatively with an image processor. Phenotypic expression of tumors of the small intestine was also studied. One hundred male Wistar rats were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 50 micrograms/ml in their drinking water for 20 weeks (group 1). Twenty male F344 rats were given methylnitrosourea (MNU) at a dose of 50 mg/kg ip twice a week for 2 weeks (group 2). Rats in group 1 were killed in week 50 of the experiment and rats in group 2 were killed in week 25. In group 1, the percentage areas of intestinal-type cells in small, medium and large adenocarcinoma of the stomach were 0.5, 2.7 and 6.6%, the differences between these values being significant (P less than 0.05-0.01). Intestinal phenotypic expression of tumor cells of the stomach is stable and the proportion of intestinal-type cells in adenocarcinomas of the stomach is higher in the larger tumors. Adenomatous hyperplasias and adenocarcinomas of the small intestine in groups 1 and 2 were all composed entirely of cells of the intestinal type. These results suggested that intestinal-type cells in adenocarcinoma of the stomach did not originate from intestinal metaplasias but from gastric-type cells in stomach adenocarcinomas.

Male Donryu rats and B6C3F1 mice were treated with dietary 3-methoxy-4-aminoazobenzene (3-MeO-AAB) (0.06% or 0.09%), and subcellular fractions of the liver were examined for ability to mutagenically activate 3-MeO-AAB and 2 amino acid pyrolysate components using Salmonella typhimurium TA 98 as a tester strain. The treatment resulted in striking induction of enzyme(s) for the mutagenic activation of these aromatic amines in rats, but the effect was smaller in mice. The enzyme(s) involved in the reaction was characterized as an isotype of microsomal cytochrome P-448.

Various human leukemoblastoid cell lines in logarithmic growth were incubated for 16 hr with 0.5 microM [3H]fluorodeoxyuridine (FdUrd) and the incorporation of [3H]FdUrd into DNA was measured. T-acute lymphoblastic leukemia (T-ALL) cell lines incorporated 2.4-7.0 times more [3H]FdUrd into newly synthesized DNA than cell lines from B-lymphoid, pre B-ALL, null cell ALL and acute myeloid leukemia cells. T-ALL cells incorporated 1.93-3.15 pmol of [3H]FdUrd nucleotides into DNA per 10(7) cells. The amount of [3H]FdUrd incorporated into DNA was inversely correlated with the activity level of uracil DNA glycosylase of the cells. On the other hand, no correlation was observed between the incorporation and the level of deoxyuridine triphosphate diphosphohydrolase of each cell line. However, the amount of FdUrd incorporated into DNA could not be correlated with the antiproliferative activity of FdUrd against these cell lines.

The modifying potential of 31 different compounds on the development of gamma-glutamyl transpeptidase-positive (gamma-GT+) liver cell lesions was compared in an in vivo short-term assay system. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine intraperitoneally and 2 weeks later were treated with test compounds for 6 weeks and then sacrificed, all rats being subjected to partial hepatectomy at week 3. Modifying potential was scored by comparing the number and area (mm2)/cm2 of induced gamma-GT+ foci with those of the corresponding control group given DEN alone. 2-Acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, phenobarbital, barbital, dipyrone and deoxycholic acid caused a significant enhancement of both the number and area of foci. 4-Acetylaminofluorene, ethionine, benzo[alpha]pyrene, disulfiram and cholic acid had a moderate enhancing effect, whereas slight, but not unequivocal, increases in gamma-GT+ foci were observed after captafol, glutathione, sodium ascorbate and taurine administration. In contrast, acetaminophen, ethoxyquin, butylated hydroxyanisole, butylated hydroxytoluene, and ethyl alcohol showed clear inhibitory effects. It is concluded that the present short-term in vivo system has practical application for the screening of modifying agents for liver tumorigenesis including hepatocarcinogens.

Alkylehter and ester derivatives of the antitumor cyclic hexapeptide RA-V obtained from the roots of Rubia cordifolia (Rubiaceae) were synthesized and bioassayed for activity against cultured tumor cells. RA-V and its n-hexylether showed significant effects against human nasopharynx carcinoma (KB), P388 lymphocytic leukemia and MM2 mammary carcinoma cells. The activity values (log 1/IC50) of ether derivatives of RA-V gave an upward parabolic or bilinear relationship when plotted against log P (P: partition coefficient determined with the 1-octanol/water system) as the carbon number of the side chain at the phenol moiety of RA-V was increased, the optimum log P values being in the range from 3.5 to 4.9. The ester derivatives showed a similar relationship, the optimum log P values being 6.3-6.7, which is higher than that of the ether derivatives. The lethal effect of RA-V on KB cells was clearly different from that of mitomycin C, and RA-V was concluded to be a "time-dependent drug" like vinblastine.

The kinetics of nitrosation of thioproline was studied. The rate of the reaction increased with decrease in pH, and was first-order with respect to nitrite concentration. The reaction rate was proportional to the concentration of total thioproline (free plus protonated), not to that of free thioproline. The initial reaction rate followed the equation: rate = k4 X [thioproline] X [NaNO2] X [H+] The rate constant was found to be 49.4M-2 . sec-1 at pH 2.0 and 37 degrees. Thioproline acted as a nitrite scavenger, and suppressed the formation of a carcinogen, N-nitroso-N-benzylmethylamine, from N-benzylmethylamine and nitrite. More than 90% of the formation of N-nitroso-N-benzylmethylamine was inhibited by adding 20mM thioproline to a reaction mixture containing 20mM N-benzylmethylamine and 20mM sodium nitrite at pH 3.0 and 37 degrees.