A sublethal dose of D-penicillamine (DP) induced hyperlipoperoxidemia and hypocupremia in old rats. Treatment of cancer cells in vitro and in vivo with DP resulted in appreciable suppression of cell multiplication and a remarkable inhibition of tumor growth. Erythropoiesis did not seem to be affected by DP. The selective effect of DP seems to have resulted from the reduced superoxide dismutase activity and/or defective Mn superoxide dismutase. ----superoxide therapy; experimental cancer; D-penicillamine In mammalian cells, two types of superoxide dismutase (SOD) are known; Cu-Zn SOD, and Mn SOD. Malignant cells are suspected of lacking Mn SOD (Oberley and Buettner 1979). Then, a selective superoxide toxicity to cancer cells can be expected if Cu-Zn SOD could sufficiently be copper-chelated. The present investigation was undertaken to see whether D-penicillamine (DP) induces any appreciably selective toxic effects on cancer cells.Fasted female Donryu rats, 6 months of age, were intraperitoneally injected with DP in a dose of 1 g/kg body weight and were bled 24 hr later. The serum copper levels, which were determined by atomic photoabsorptiometry, were 1.68+0.38 µg/ml (mean+s.D.) for 10 untreated rats and 1.22+0.26 for 13 DP-treated (p<0.01). Plasma lipoperoxide concentrations determined by Yagi's method (1976), as expressed in terms of malondialdehyde, were 2.08+0.60 for 4 untreated and 3.70+1.03 for 5 DP-treated rats (p<0.01). Thus, DP increases the superoxide radicals.The FM3A adenocarcinoma cells from C3H mouse were cultured in MEM medium supplemented with 10% calf serum. Fig. 1 shows that there is a small fraction of cells that are sensitive to DP, and that most of the cells are more or less resistant as estimated at 48 hr of DP.Fifteen Donryu rats, 10 weeks of age, were implanted in the right footpad with AH 109A adenocarcinoma cells and therapeutic effects of DP were evaluated as described elsewhere (Okuyama 1978). Eight of the 15 were intraperitoneally injected with DP (1 g/kg) on day 3 of the implantation. The tumor growth by weight 5 days later was inhibited to 70% of the saline control (p<0.005).Effects of DP on the cell renewal system i.e., on hemopoiesis in the rat femoral marrow, were tested. There was no significant difference in the cellularity, myeloid/ erythroid ratio (1.58 +0.32 vs. 1.79 +0.13) or erythroid mitotic index (1.86+0.70 vs. 2.20+ 0.54) between the DP-treated (3 rats) and nil control (3 rats) as studied on day 6 of DP in a dose of 1 g/kg.The present experimental data suggest that cancer cells are more vulnerable to DP
The formation of radical ions in γ‐irradiated polymethyl‐methacrylate (PMMA) matrices at 77°K and thermal‐induced reaction of these radical ions were of studied by optical absorption spectroscopic measurements. The radical ions of stilbene and pyrene were investigated. These radical ions decay according to second‐order kinetics, which means that the neutralization reaction of the cationic species and anionic species participates in the decay process. The kinetic plots consist of two straight lines; that is, fast and slow decay processes are concerned. The activation energies were estimated to be Efast = 2.4 kcal/mol and Eslow = 6.4 kcal/mol, respectively. The probability of recombination reaction depends on the distance between cationic and anionic species.
To improve the spatial and density resolution of Compton radiography, the authors utilized direct magnification with a pin-hole collimator and contrast magnification with the Shinozaki color TV system, a digital color display. Great improvement was attained in spatial resolution. Contrast magnification resulted in sharp delineation of soft-tissue lesions including cancer and its infiltrations into normal surrounding breast tissue. It is expected that in the future, Compton radiography will have wide raiological application with reduced radiation dosage.
The induction of redifferentiation of cancer cells was studied. This was achievable with bestatin, especially in combination with sex hormones or prostaglandin D2, in murine undifferentiated mammary adenocarcinoma cells in vitro. Prostaglandin D2 also exerted a similar redifferentiating effect on M1 murine leukemia cells and a consecutive bestatin-hormone regimen was effective in endocrine tumors in man. Cancer redifferentiation may one day be developed into a clinical technique.
A 70-year-old man having severe ischemic heart diseases developed bilateral, duplicate lung cancer of large cell and squamous cell types. Chemoimmunotherapy consisting of carmofur, picibanil inhalation, i.m. sizofilan, and peroral bestatin was started, and 3 months later, peroral mdroxyprogesterone acetate was added. The tumor regressed, and the patient survived more than 34 months. This type of nonaggressive regimen may thus be useful for tumors other than adenocarcinomas, too.bestatin ; carmofur ; lung cancer ; mdroxyprogesterone acetate In order to exploit its possible anti-cancer effect, mdroxyprogesterone acetate (MPA) was administered at a high dosage on a man of 70 years of age who had been found to have bilateral, duplicate lung cancer : large cell carcinoma in rB6 (right hilar mass), and squamous cell carcinoma in 1B3 (not visible on the chest x-ray) (Fig.
In order to attest the evolutionary hypothesis of non-epithelialepithelial tumor shift (Okuyama and Mishina 1986), the published cancer incidence data for the population of Nagasaki City during the period of 1973-1977 was studied along with appropriate control populations of Fukuoka City, and Miyagi and Osaka prefectures. Significant increments of non-epithelial tumors including leukemias, and epithelial tumors such as cervical cancers and choriocarcinomas were observed. An inference was made to the post-atomic bomb radiation carcinogenesis that different organ systems responded to that irradiation with different oncogenic patterns : Neoplasms of the pre-vertebral organs (non-epithelial organ systems) were the first to react and tapered long (curve type I) ; Tumors of the vertebral but pre-mammalian (those of the digestive tract, respiratory and thyroid) could have formed two separate peaks, one for the early and high dosage and the other for the late and low dosage (II) ; With breast cancer or the mammalian symbol tumor, there was a single peak reflecting the cohort of reproductives (III). The evolutionary and phylogenetic progression could have taken place from I through III. Thus, cancer incidence analysis may be helpful in deciphering the atomic bomb radiation carcinogenesis. atomic bombing ; evolutionary concepts of cancer ; late cancer incidence ; radiation carcinogenesis When we examined the epidemiological aspects of cancer based on the published WHO data (Waterhous et al. 1982), there seemed to be a predominance of non-epithelial tumors during the period of infancy to adolescence, and that of epithelial ones thereafter (non-epithelial-epithelial tumor shift) (Okuyama and Mishina 1986). In the hope of obtaining an insight into the underlying evolutionary mechanisms, the epidemiological studies were expanded to include the population of Nagasaki City 30 years after the atomic bombing. In spite of probable dilution of the fraction of the atomic bomb survivors, the investigation was thought valid enough because the radiation is penetrating, and because carcinogenetic manifestation of radiation would take quite a long time. The results were thought to imply that the atomic bombing may possibly still have a hold on that victim population.
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