Comparative effects of 1, 10-phenanthroline and 1, 7-phenanthroline on DNA and RNA synthesis in mouse spleen

When 1, 10-phenanthroline at 10^?4 mole/kg was administered intraperitoneally to C3H mice, a significant decrease of (³²P) Na₂HPO₄ incorporation into splenic DNA and RNA was noted within 15 min. The same dose or higher was required to significantly inhibit the incorporation of (5-³H) uridine and (methyl-³H) thymidine into splenic nucleic acid. 1, 10-phenanthroline also decrease the incorporation of the ³²P into DNA and RNA in 6C3HED ascites tumor. 1, 7-phenanthroline, a non-chelating analogue at 10^?4 mole/kg, less effectively altered the rate of the ³²P incorporation into splenic nucleic acid within 15 min, but significantly inhibited the incorporation within 1 hr.     

Environmental carcinogenesis: an integrative model.

An integrative theory is proposed in which environmental carcinogenesis is viewed as a process by which the genetic control of cell division and differentiation is altered by carcinogens. In this theory, carcinogens include physical, chemical, and viral "mutagens," as well as chemical and viral gene modulators. Existing explanations of carcinogenesis can be considered either as somatic mutation theories or as epigenetic theories. Evidence seems to support the hypothesis that both mutations and epigenetic processes are components of carcinogenesis. The mutational basis of cancer is supported by the clonal nature of tumors, the mutagenicity of most carcinogens, high mutation frequencies in cells of cancer-prone human fibroblasts lacking DNA repair enzymes, the correlation of in vitro DNA damage and in vitro mutation and transformation frequencies with in vivo tumorigenesis, age-related incidences of various hereditary tumors, and the correlation between photoreactivation of DNA damage and the biological amelioration of UV-induced neoplasms. Since both mutagens and gene modulators can be carcinogenic it may be that carcinogens affect genes which control cell division. An integration of the mutation and epigenetic theories of cancer with the "two-stage" theory and Comings's general theory of carcinogenesis is proposed. This integrative theory postulates that carcinogens can affect regulatory genes which control a series of "transforming genes." A general hypothesis is advanced that involves a common mechanism of somatic mutagenesis via error-prone repair of DNA damage which links carcinogenesis, teratogenesis, atherosclerosis and aging. Various concepts are presented to provide a framework for evaluating the scientific, medical, and social implications of cancer.     

Isolation and identification of pathogenic Naegleria from Florida lakes.

Five cases of primary amoebic meningoencephalitis associated with swimming in freshwater lakes have been recorded in Florida over the past 14 years. The present study demonstrated that pathogenic Naegleria, the causative agent, is relatively widespread. Twelve of 26 lakes sampled only once yielded the amoeba. Populations in three of five lakes sampled routinely reached levels of one amoeba per 25 ml of water tested during the hot summer months. Overwintering in freshwater lake bottom sediments was demonstrated, showing that thermal-discharge pollution of waters plays a miniscule, if any, role in the maintenance of pathogenic Naegleria in nature in this semitropical area.     

Stimulative effect of prostaglandins on production of hexosamine-containing substances by cultured fibroblasts (2) early effect of various prostaglandins at various doses

Early effects of various prostaglandins on the production of hexosamine-containing substances by cultured fibroblasts, which were derived from a rat carrageenin granuloma, were studied. At the stationary phase, the cells were exposed for 6 h to one of the prostaglandin A₁ (PGA₁), A₂, B₁, B₂, D₂, F_1α, F_2α, E₁, E₂ or arachidonic acid in various concentrations ranging from 0.01 to 10 μg/ml for all the stimuli and from 10 pg to 10 μg/ml for PGF_2α. The activity of the cells in incorporating ³H-glucosamine into hexosamine-containing substances (acidic) glycosaminoglycans and glycoproteins) during this period was compared with that of control cells. All the stimuli tested showed more or less stimulative effect on the synthesis of hexosamine-containing substances at their specific concentrations. PGF_2α was found to be the most potent stimulant and its stimulative effect was found significant even at the low concentration of 100 pg/ml. PGD₂, F_1α and E₂ were the next potent stimuli. Their optimum dose were around 1 μg/ml but they still had significant stimulation at the concentration of 0.01 μg/ml. Effect of PGE₂ was rather mild. Stimulation by PGA₁, A₂, B₁ and B₂ or arachidonic acid was seen at high dose, and its seemed to be non-specific. The results suggested that these prostaglandins such as PGF_2α, D₂, F_1α and E₂ play some important role on regulating the production of intercellular ground substances.     

Thromboxane B2 transformed from arachidonic acid in carrageenin-induced granuloma

A main product (PI) transformed from arachidonic acid in carrageenin-induced granuloma in rats was structurally analysed. PI was converted to a more polar substance by the reduction with sodium borohydride. On the basis of the data on gas chromatography-mass spectrometry, its structure was identified with the hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12-heptadecadienoic acid (Thromboxane B2)     

Stimulation by prostaglandin F2α of acidic glycosaminoglycan production in cultured fibroblasts

The effect of PGF2α on the synthesis of hexosamine-containing substances (acidic glycosaminoglycans and glycoproteins) was studied in cultured fibroblasts derived from a rat carrageenin granuloma. Treatment with PGF2α ranging from 0.01 μg/ml to 20 μg/ml resulted in a significant increase of the production of these macromolecules by the cells. The stimulatory effect was found significant even at the low concentration of 10 ng/ml, and could be seen as early as 3h after exposure to PGF2α. The hexosamine-containing substances increased by PGF2α revealed that 80% of the increase was due to acidic glycosaminoglycans and the rest was due to glycoproteins.     

Somatic embryogenesis and plant regeneration in an interspecific hybrid of Oryza

An embryogenic callus was obtained from immature panicle of an interspecific hybrid (Oryza sativa x O. latifolia) F₁. The medium consisted of HE salts supplemented with 2,4-D, NAA (each 2 mg/l), kinetin (3 mg/l), yeast extract (1360 mg/l) and casein hydrolyzate (300 mg/l). The callus was milk-white in colour compact and granulate in texture. Various developmental stage of embryoid, such as globular, heart-shape, scutellum-shape and mature embryoid were observed in an embryogenic callus. Plantlets were successfully regenerated from 1-month-old callus with more than 80% regenerational frequency in each subculture for 12 passages.     

Characterization of two enzyme proteins catalyzing NADP+/NADPH-dependent oxidoreduction of prostaglandins at C-9 and C-15 from swine kidney

Two proteins (pI 4.8 and 5.8) capable of catalyzing NADP⁺/NADPH-dependent oxidoreduction of prostaglandins at C-9 and C-15 but not at C-11 have been purified to homogeneity from swine kidney. Both proteins exhibited identical molecular weight and subunit size. Similar amino acid composition, antigenic determinants, and coenzyme and substrate specificity were also found. The molecular weight of the enzyme as determined by gel filtration was 29,000. Electrophoresis in sodium dodecyl sulfate-polyacrylamide gel gave a value of 29,500 indicating the presence of a single polypeptide chain. Either enzyme protein utilized a variety of prostaglandins (PGS) as substrates. PGA₁-glutathione conjugate and PGB₁ were found to be the best substrates for prostaglandin 9-ketoreductase and 15-hydroxyprostaglandin dehydrogenase activities, respectively. For prostaglandins having dual reactive groups in a single molecule, the rate of oxidation of PGF_2α at C-15 was comparable to that at C-9, whereas the rate of reduction of 15-keto-PGE₂ at C-15 was far greater than that at C-9.     

Replication variants of the human inactive X chromosome

The sequence of DNA replication was studied within the inactive X chromosome in human lymphocytes, by means of the FPG method. Several variants of the replication sequence were found. The number of variants in the cells of a single donor exceeded 2 in each of the 4 normal individuals studied. The phenomenon is discussed with respect to the regulation of DNA synthesis and to the cell differentiation process.