Chronological changes in ceruloplasmin oxidase activity after γ-irradiation with semilethal doses of 3-5 Gy, were investigated in four mammalian species; rat, guinea pig, lamb and pig. The ceruloplasmin activity increased soon after irradiation but later decreased. Although the extent of the increase and its time-course varied among species, it was most remarkable in rats and least so in guinea pigs, with the highest activity generally attained at 12 h after irradiation. In contrast, erythrocyte and leukocyte counts decreased after irradiation, and showed minimum values when ceruloplasmin levels were maximum. These results suggest that ceruloplasmin is involved in the recovery from radiation disease.

View full abstract

When 125 μM Fe²⁺/EDTA treated plasmid pUB3 was used to transfect an Escherichia coli NKJ2004 (nth nei) host, which is totally defective in glycosylases for thymine glycol and 5-hydroxycytosine, a 3.7 fold increase in mutation frequency was observed. Among 46 supF mutants sequenced, 28 had base substitutions, with G:C→C:G transversion predominant (14 cases), followed by G:C→T:A transversion (6 cases) and G:C→A:T transition (6 cases). The results are consistent with our previous Fe²⁺ mutagenesis results where, in the wild type host, 78% were base substitutions, with G:C→C:G transversion (59%) predominant, followed by G:C→T:A transversion (28%) and G:C→A:T transition (11%). Treatment of pUB3 DNA with Fe²⁺/EDTA did not yield formation of Endonuclease III sensitive sites. The possibility of 5-hydroxycytosine as the causative lesion for Fe²⁺ induced G:C→C:G transversion is discussed.

View full abstract

Electron spin resonance (ESR) of tooth enamel is a recently developed method for the retrospective dose estimation of human radiation exposures. The assay requires isolation of enamel from dentin, which is difficult because the boundary between enamel and dentin is not easily discernible. Here we describe a simple method for isolating enamel by alkaline denaturation of dentin. The method requires 4 weeks, but scratching of the denatured and hence softened dentin is needed only once a week. Above all, no special skill is required. We found that the alkaline treatment did not cause deterioration of the ESR signal recorded in enamel exposed to 2 Gy of γ rays prior to its isolation. The assay is particularly suited for teeth containing many cracks that were generated during long-term storage after extraction of the teeth. Such teeth tend to disintegrate during enamel isolation processes, which poses difficulties to isolate enamel mechanically from individua small pieces

View full abstract

While recent advances in elucidating the enzyme/substrate relationship of phosphorylation cascades have demonstrated several distinct pathways in membrane-cytoplasm signaling, the molecular dissection of p53 and the products of other proto-oncogenes have greatly promoted the studies of nuclear signaling and expanded the checkpoint concept to mammalian cells. The growing list of p53-activating factors ranges from genotoxic agents to non-genotoxic stresses. The diverse involvement of p53 and its close linkage to other nuclear and extranuclear signaling networks force us to reconsider the concept of cellular stress response. A signaling network emerges from crosstalks between different types of stress in the same signaling pathway and crosstalks between different pathways in response to the same stress. We review the present knowledge on cellular stress signaling with emphasis on the crosstalks between different pathways and the molecules which mediate these crosstalks and offer our concept of signaling checkpoints. The importance of stress signaling checkpoints in cancer evolution and cancer therapy is also discussed.

View full abstract