Gan最新文献

A subline of human KB cells that was resistant to 1-beta-D-arabinofuranosylcytosine (ara-C) was established by continuous exposure of the cells to increasing concentrations of ara-C. Thirteen resistant clones were isolated from the resistant subline (KB/ara-C). KB/ara-C showed 1,300-fold higher resistance than the parent KB cells to ara-C; the most resistant clones, clones 7 and 10, showed 1,330-fold higher resistance. In the absence of ara-C, the resistance of the parent KB/ara-C cells was stable for at least 14 weeks, whereas that of clone 7 was stable for 10 weeks, but was slightly less after 14 weeks. The ara-C kinase and ara-C deaminase activities of the 13 clones and the cellular uptake of ara-C by several clones were measured. In general the clones showed decreased deoxycytidine kinase activity and decreased cellular uptake of ara-C. Most clones had higher cytidine deaminase activity than KB cells, but some had activity similar to that of the KB cells. A clear inverse relationship was found between the ara-C sensitivity of the clones and their kinase activity, but not their deaminase activity or their ara-C uptake. These results clearly demonstrate that a major mechanism of ara-C resistance of these human KB cells was a decrease in the activity of the ara-C activating enzyme deoxycytidine kinase. The parent KB/ara-C cells showed no clear cross-resistance to various antitumor agents other than an ara-C derivative, including metabolic inhibitors, alkylating agents, DNA binders and mitotic spindle poisons.

B-cell lines which showed predominantly surface IgA kappa immunoglobulins were established from each of seven adult T-cell leukemia (ATL) patients. ATL virus proviral DNA was found in five of the lines. Though the chromosomal analysis of the B-cell lines yielded normal results, fresh leukemic T-cells showed chromosome abnormalities.

A mouse hybridoma cell line, H15, produced monoclonal antibody reacting with all the adult T-cell leukemia (ATL) virus (ATLV)-bearing cell lines but none of the ATLV-negative cell lines tested. Binding of H15 antibody to ATLV-bearing cell surfaces was specifically blocked by anti-ATLV positive human sera. Radioimmunoprecipitation analyses revealed that the antigen detected by H15 antibody was p24, a core protein of ATLV. Pulse-chase experiments using H15 antibody led to the identification of a protein, p53, which could be a precursor of p24.

Various polyphenols and aminophenols were tested for reactivity with deoxyguanosine and DNA in the presence of hydrogen peroxide and ferric ion. Deoxyguanosine was efficiently hydroxylated at the C-8 position by these treatments. In the case of DNA, strand scission was observed in addition to the hydroxylation of guanine residues.

In vitro and in vivo cross-resistance to mitoxantrone of two vincristine-resistant sublines of P388 leukemia with different degrees of resistance in vitro was compared with that to adriamycin. A subline with a lower degree of resistance to vincristine exhibited approximately the same responses in vivo to mitoxantrone and adriamycin as the original P388 leukemic cell line, although it was evidently cross-resistant in vitro to these agents. Another subline having a higher degree of resistance to vincristine showed a 25-fold cross-resistance in vitro and gave no response in vivo to adriamycin. With mitoxantrone, on the other hand, this subline was solidly resistant as compared with the sensitive line but still retained significant responsiveness in vivo irrespective of a 150-fold cross-resistance in vitro. These results suggest that cross-resistance on a cellular basis does not necessarily correspond to in vivo cross-resistance. The relationship between in vitro and in vivo cross-resistance is discussed.

The mortality from cancer, excluding gastric stump cancer, was examined in 3,827 Japanese patients who had undergone partial gastrectomy for benign gastroduodenal diseases. Although no increase in gastric stump cancer had been found in a previous analysis, the number of deaths from liver, lung and colorectal cancer was significantly greater than expected. The mortality rate was also significantly increased in patients with cirrhosis of the liver. Postoperative hepatitis, intestinal stasis and/or increased bacterial growth after Billroth II gastrectomy were considered as possible causes of the high mortality.

The inhibitory effects of hemin on the mutagenic activities of 1,3-, 1,6- and 1,8-dinitropyrenes (1,3-,1,6- and 1,8-DNPs) were investigated in Chinese hamster V79 cells. Mutant cells were selected on the basis of their resistance to ouabain. Hemin itself did not have any cytotoxic effect on Chinese hamster V79 cells, and did not induce mutations when added at a concentration of 10 micrograms/ml. The mutagenic activities of 1,3-, 1,6- and 1,8-DNPs were inhibited dose-dependently by hemin and were reduced 91.7%, 95.7% and 94.7%, respectively, by the highest concentration of hemin tested (10 micrograms/ml).

The future trend in male lung cancer mortality in Japan was predicted by using a simulation model. The model was based on the age-specific death rates from lung cancer in males by birth cohort, expressed as Fi(t) = rkSitr-1 exp(-ktr). The parameters in the function were obtained from the mortality data in Vital Statistics (1960-1980). The chi-square test for goodness-of-fit supported the statistical validity and acceptability of the function. Extrapolation of the function provided future age-specific death rates by birth cohort for males in Japan. In this simulation model it was possible to evaluate the effects of preventive strategies and/or therapeutic improvements on lung cancer mortality when five additional parameters were taken into consideration. According to this model, the age-adjusted death rate from lung cancer in Japanese males is predicted to increase linearly until the year 2000 and to level off thereafter. The total number of deaths from lung cancer for all Japanese males is predicted to be 27,000 in 1990 and over 40,000 in 2000. With the establishment of an effective preventive strategy for young generations, the mortality would begin to decrease a few decades later. Improvements in the therapy of lung cancer, if realized, might suppress the future upward mortality trend in Japan to some extent. The above simulation model based on birth cohort analysis should be useful in estimating the impact of developments in prevention and treatment of lung cancer as well as in predicting the future mortality trend.

A population of cells that responds to colony-enhancing factor has been reported to constitute the most immature subpopulation in the compartment of granulocyte/macrophage progenitors (GM-CFC). A similar colony-promoting activity (CPA) was found in the supernatant of long-term cultures of murine bone marrow cells. Here, some characteristics of the cells responsive to CPA were studied. The CPA-responsive cells in the spleen and bone marrow of W/WV mice were as numerous as in +/+ litter-mates. The concentration of CPA-responsive cells was independent of those of other cell populations, namely pluripotent stem cells (CFU-S), pluripotent precursor cells in vitro and GM-CFC in the spleen and bone marrow. Seeding efficiency in the spleen of irradiated mice and the cell-cycle state of CPA-responsive cells also differed from those of CFU-S and GM-CFC. Accordingly, the target of CPA appears to constitute a separate compartment in the progenitor populations of granulocytic lineage.

Synthetic porphyrin (Fe) intercalators cleave DNA at guanine-cytosine and guanine-thymine sequences. The specificity for cleavage of base sequences of DNA is quite similar to that of bleomycin.