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.

View full abstract

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.

View full abstract

A 10-year prospective cohort study was made of 495 male hepatitis B surface antigen (HBsAg) carriers aged over 40 at entry. The observed/expected mortality rate ratio of primary liver cancer (PLC) was 10.40, based on the general population in Japan. The annual incidence rate of PLC (including 2 survivals) was 365/100, 000 person-years. All histologically confirmed cases of PLC were hepatocellular carcinoma (HCC). The chronic HBsAg carrier state is suggested to be a risk facter of HCC.

View full abstract

The inhibitory effects of heroin 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 10μg/ml. The mutagenic activities of 1, 3-, 1, 6- and 1, 8-DNPs were inhibited dose-dependently by hemin and were reduced 1.7%, 95.7% and 94.7%, respectively, by the highest concentration of hemin tested (10μg/ml).

View full abstract

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)=rkSit^r-1 exp(-kt^r). 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.

View full abstract

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.

View full abstract

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. Radioimmunopre-cipitation 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.

View full abstract

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/W^V 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.

View full abstract

The present study deals with the influence of presensitization with tumor antigens via the intragastric route on the development of syngeneic tumor-specific immunity. Tumor-specific T cell-mediated immunity could be induced in C3H/He mice by intradermal inoculation of syngeneic X5563 tumor cells, followed by the surgical resection of the tumor 7 days later (immunization procedure). However, when the mice were presensitized intragastrically (ig) with 10⁸ X-irradiated (10, 000R) tumor cells for four consecutive days, these mice failed to show in vivo protective immunity even after the above immunization procedure. Winn assays performed with spleen cells from mice presensitized ig with X5563 tumor cells revealed that ig-induced suppression was specific for the tumor antigen used for the presensitization, and that suppressor cell activity was not detected in the induction or implementation of in vivo tumor-specific effector cell activity. It was also demonstrated that such unresponsiveness was accompanied by failure to develop delayed-type hypersensitivity and cytotoxic T cell responses to X5563 tumor antigens. These results are discussed in the light of the effect of presensitization with tumor antigens via inappropriate routes on the subsequent induction of in vivo tumor-specific immunity and in relation to the tumor escape mechanism which could occur in gastrointestinal cancers.

View full abstract

The action mechanism of antibody-dependent macrophage-mediated cytotoxicity (ADMC) induced by OK-432 against MM2 carcinoma cells was examined. Adherent peritoneal exudate cells (adherent PEC) harvested from mice 4 days after intraperitoneal injection of OK-432 exhibited potent cytotoxic activity against MM2 cells in the presence of anti-serum obtained from tumor-free mice which had survived over 60 days following treatment with OK-432 and resisted rechallenge with MM2 cells. The cytotoxic activity of the adherent PEC was not abolished by treatment with anti-Thy-1.2 and complement, and there were no differences in ADMC between adherent PEC from BALB/c mice and those from athymic BALB/c (nu/nu) mice. Further, ADMC activity was shown not only against MM2 cells, but also against other allogeneic tumor cells, such as MOPC-11 plasmacytoma cells. On the other hand, the effective factor(s) in anti-serum to MM2 cells was eliminated by passage through a protein A-Sepharose CL-4B affinity column. The action mechanism of ADMC caused by the adherent PEC and anti-serum to MM2 cells is discussed.

View full abstract

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.

View full abstract

A potent interferon (IFN) inducer, 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP), induced hyporeactivity in mice, and so IFN induced by subsequently administered ABPP was reduced even 120hr after the first administration of ABPP. This hyporeactivity was counteracted by the injection of IFN (10, 000IU or more) 3hr before the subsequent administrations of ABPP. Since the injection of more than 5, 000IU/ mouse of IFN 3hr before an administration of ABPP enhanced the circulating IFN titer, the priming effect in vivo by IFN may result in the reduction of hyporeactivity. Administrations of ABPP (200mg/kg or 500mg/kg) at intervals of 2 days and the injection of IFN (25, 000IU/mouse) 3hr before each administration of ABPP to neuroblastoma-bearing A/J mice reduced the mortality and completely cured 40% of the mice in each combined therapy group. These results suggest that the combined use of the IFN inducer with IFN may be available for patients with neoplasm or viral nfection.

View full abstract

With the aim of establishing a topical chemotherapy against stomach carcinoma, 5-fluorouracil (5-FU) emulsion (oil/water type) for injection has been developed. The drug distribution was analyzed by 5-FU bioassay and radiographic examination of soft parts, for which radiopaque Lipiodol was employed in an oil phase. In order to examine local toxicity, tissue retention, and transfer to lymph nodes of 5-FU emulsion, the drug was administered perorally to rats and injected intramurally through the gastric serosa into laparotomized dogs. Following this series of experiments, which gave satisfactory results, the time courses of drug concentration in the gastric wall and regional lymph nodes were studied as a pre-clinical trial, by applying endoscopic intramural injection of 5-FU emulsion or solution in dogs. The anti-metastatic and anti-neoplastic effects of 5-FU emulsion were investigated in an experimental model of lymph node metastasis in mice. The emulsion was more effective in subduing metastasis and tumor growth than the solution, and the effectiveness of the former was further augmented by the use of repeated injections rather than a single injection. This method of endoscopic injection of 5-FU emulsion should be of great value as a local therapeutic measure against stomach carcinoma itself as well as against metastatic lesions in the lymph nodes.

View full abstract