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We investigated how the nutrient status of Matsushima Bay was affected when a wastewater plant was destroyed by a tsunami in March 2011. The nutrient concentrations in the seawater and the treated water from the wastewater plant increased just after the tsunami, but decreased again to pre-tsunami levels after 2013. The amount of untreated water that passed through the wastewater plant decreased just after the tsunami. It was estimated that approximately 40.7 × 103 m3/day of the treated water from the wastewater plant was discharged to Matsushima Bay; therefore, the quantity of effluent from the wastewater plant was less than one percent of the water inflow from Takagi River and Sendai Bay (which are outside Matsushima Bay) to Matsushima Bay. The nutrient concentrations of seawater in Sendai Bay were lower than those in Matsushima Bay. The results suggest that nutrient concentrations in Matsushima Bay after the tsunami did not increase because any untreated or poorly treated effluent was easily diluted by the river flow and the inflow of seawater. Many people were concerned about eutrophication, therefore, because of the decreased functioning of the wastewater plant in Matsushima Bay. Marked eutrophication in the bay was not observed after August 2011.

Two sediment cores were collected from two sites in Nagatsura-Ura Lagoon, the mouth of which was destroyed in the 2011 Tohoku-oki tsunami. Although sediment conditions differed widely between the central and inner parts of the lagoon, we could identify traces of the 2011 Tohoku-oki tsunami at both, and those of earlier tsunamis in the inner part of the lagoon. Chlorophyll a maxima were observed at core depths between 62 and 72 cm in the central part of the lagoon. We inferred that this horizon correlated with the 2011 Tohoku-oki tsunami deposit. In the inner part of the lagoon, the horizon at core depths of 116—142 cm could be aged to the 1400s, and is thus thought to have been formed as a consequence of the Kyotoku earthquake of 1454. The dinoflagellate Alexandrium spp. accounted for ~ 22.6% of the total read numbers of phytoplankton from next generation sequencing. Diatoms made up the second largest group of phytoplankton, with Chaetoceros spp. representing ~ 10.5% of the total. The vertical profiles of dinoflagellate and diatom compositions showed little change. Although traces of tsunamis were observed in cores from the lagoon, and in nearby closed bays, we believe that the microbial composition has changed only slightly in the lagoon due to poor seawater exchange through the closed lagoon mouth.

Recent declines of macroalgal forests due to climate change imply that the aquaculture production of macroalgae may also be negatively affected by ocean warming. It has previously been shown that nutrient enrichment can offset the negative impact of warming on the survival and growth of the cultivated macroalga Undaria pinnatifida, although it can also increase the risk of herbivory by unrecognized mesograzers. Observations of several hundreds or thousands of the isopod Cymodocea japonica around U. pinnatifida cultivation ropes in autumn, prompted the analysis of their size-frequency distribution, relationship between body size and consumption rate, and combined effects of elevated temperature and nutrient enrichment on the consumption rate of the algae by the isopod in the current study. Although the body size of the isopods collected in autumn was smaller than those collected in winter and spring, the consumption rate of 600 small isopods was similar to the rate of a large individual. Additionally, the consumption rate doubled in response to an increase in temperature from 15 to 18°C and nutrient enrichment, and tripled with their combination. These results suggest that ocean warming combined with nutrient enrichment increase the risk of herbivory during U. pinnatifida cultivation, especially during isopod outbreak periods.

Phytoplankton assemblages are important for understanding the quality of primary production in marine ecosystems. Here, we describe development of a methodology for monitoring marine phytoplankton assemblages using an in situ multi-wavelength excitation fluorometer (MEX) and its application for seasonal observations in coastal and offshore areas around Japan. The MEX recorded the fluorescence excited with nine light-emitting diodes, temperature, and sensor depth. We prepared reference datasets comprising temperature, MEX fluorescence, and plant-pigment-based chemotaxonomy phytoplankton assemblages. Target MEX fluorescence was decomposed by reference MEX fluorescence using a linear inverse model for calculating coefficients after the reference data were limited by temperature, followed by reconstruction of plant-pigment-based chemotaxonomy of the target MEX fluorescence using the coefficients and the chemotaxonomy assemblages of the reference data. Sensitivity analysis indicated poor estimation of the proportion and/or chlorophyll a-based abundance of chlorophytes, haptophytes, prasinophytes, and prochlorophytes; however, limiting the estimations to five chemotaxonomic groups [diatoms, dinoflagellates, cryptophytes, cyanobacteria (cyanophytes and prochlorophytes), and other eukaryotes (chlorophytes, haptophytes, and prasinophytes)] resulted in positive correlations of both the proportion and abundances, suggesting that the five taxonomic abundances were well-estimated using the MEX. Additionally, MEX observations denoted spatial and seasonal variations of phytoplankton assemblages, with high contributions from other eukaryotes in every area and season, cyanobacteria highly during the summer in surface Kuroshio and Japan Sea waters, and diatoms in the Oyashio and Oyashio–Kuroshio transition areas and the Okhotsk Sea. Furthermore, ratios of water-column-integrated chlorophyll-based abundances to those on the surface at the chemotaxonomy group level were differed among the areas and groups. These findings suggested that phytoplankton-assemblage monitoring in the vertical direction is essential for evaluation of their current biomass, and that the MEX promotes the acquisition of these observations.

We investigated water temperature, Chlorophyll a (Chl a) concentration, and oyster growth from April to December in 2014, 2016, and 2017 in Nagatsuraura Bay, Miyagi Prefecture, Japan. We also calculated the remaining phytoplankton biomass by subtracting total filtration of oysters in aquaculture areas. We estimated that suitable oyster culture density is when that value is positive. Water temperature was high in summer, exceeding 20 °C from mid-June to mid-September. Chl a concentration gradually increased from April through July, and remained high from July through September, before decreasing after October. Maximum Chl a exceeded 9 µg/L in the water column. In Nagatsuraura, which is a closed bay, the periods of phytoplankton bloom from Spring forward were longer than in open or semi-open bays. Therefore, Nagatsuraura oysters grow more quickly than those in open or semi-open bays. Oyster growth varied with the season. Although periodic weight loss by egg-laying was predicted from July to October, oyster weights tended to increase easily during this season compared with other periods. The mass balance of oyster feed in the aquaculture was calculated based on phytoplankton amount > 0 in most periods. As values were phytoplankton biomass in an aquacultural area > amount required by oysters, we inferred that Nagatsuraura is not deficient in oyster food. With the post-tsunami retirement of many fishery employees, and reduction in the number of oyster culture companies, the total quantity of oysters in the aquaculture grounds has decreased. As a result, the aquaculture grounds are not currently overcrowded.

We investigated two sediment cores to understand whether a tsunami in Onagawa Bay, Japan caused environmental changes. The value of δ13C ranged from −21.9‰ to −24.3‰ and of δ15N ranged from 5.1 to 5.9‰. We conclude that the source of the sediment in the present study area was mainly oceanic and not terrestrial. The chlorophyll concentration ranged from 1.8 to 4.0 μg/g ww, and did not vary greatly between surface and bottom layers. We inferred that all layers were deposited after the tsunami. The major phytoplankton taxa in sediments were diatoms from DNA sequencing. The presence of harmful dinoflagellates was minor. The concentrations of several heavy metals decreased slightly after the tsunami. We inferred that heavy metals in sediments were diluted by the tsunami disturbance. The land in Onagawa suffered serious damage, but disturbance of the seabed was much less evident.

We assessed the feasibility of retrospectively reconstructing phytoplankton assemblages using next-generation sequencing of the Psb A gene from cryopreserved DNA sampled from Ofunato and Yamada bays during the bloom season before (May–August 2010) and after (June–July 2011) the tsunami. The total number of phytoplankton species detected was >280 when the operational taxonomic unit (OTU) similarity threshold was set at 0.95. During the investigation, the sequences of Bacillariophyta, which are considered a suitable food for oysters, comprised >50% of the phytoplankton composition in both bays. Chlorophyta, mainly pico-Prasinophyceae, which are too small for oysters, comprised 30%. Chroomonas sp. (ex Dinophysis acuminata), Geminigera cryophila, Teleaulax amphioxeia, and Cryptophyta sp. (CR-MAL11), which have relation to diarrhetic shellfish poisoning, were predominant in the Cryptophyta. Dinophysis spp. were the predominant Dinophyceae species, and cause diarrhetic shellfish poisoning. Because these phytoplankton species are unsuitable oyster food, we think that continuous monitoring of species is necessary. After the tsunami, the beta diversity using unweighted UniFrac in Ofunato Bay tended to differ from those before the tsunami. The ratio of predominant of Bacillariophyta species tended to decrease after the tsunami, the number of minor species detected in each taxon tended to increase. We infer that the temporary change was caused by the multiple environmental changes, such as the resuspension of cysts and phytoplankton deposited in the seabed, destroyed local sewage infrastructure, breakwater, and many oyster rafts.

Color is one of the important factors that determine the commercial value of cultivated marine macroalgae such as the brown alga Undaria pinnatifida (Laminariales; Phaeophyta) in Japan. Macroalgal color is fundamentally derived from the algal photosynthetic pigment content, which is affected by abiotic factors. However, little is known about the quantitative relationship between pigment content and color and the direct effects of abiotic factors on the color of marine macroalgae. We conducted a 24-day indoor culture experiment to assess the combined effects of nutrient availability (enriched and nonenriched seawater), seawater temperature (15 and 5 °C), and irradiance (180 and 30 μmol photons m−2 s−1) on the concentrations of six pigments (chlorophyll (Chl) a, Chl c 1, Chl c 2, fucoxanthin, violaxanthin, and zeaxanthin) and three color values (lightness L*, redness a*, and yellowness b*) of U. pinnatifida sporophytes. Negative correlations between pigment content and color values of the cultured algae were detected. Reduced nutrient availability, decrease in temperature, and elevated irradiance resulted in decreased pigment contents and increased color values. Moreover, a significant interaction between nutrient availability and temperature indicated that the positive effect of nutrient enrichment was antagonized by a decrease in temperature. These results suggest that U. pinnatifida can discolor under nutrient-poor, winter temperature, and saturated irradiance conditions. To increase the commercial value of this species, artificial nutrient enrichment during spring or cultivation from a deeper depth may be effective.

We investigated regular oyster dietary conditions, and shellfish and periphyton growth from 2013 to 2014 in Oginohama Bay, Miyagi Prefecture, Japan. We calculated phytoplankton biomass in the aquaculture areas minus the total phytoplankton filtration by oysters and periphyton. We estimated that the suitable oyster culture density is when that value is >0. The mass balance of phytoplankton biomass for food availability increased from January through April, and decreased from May to June. Although the mass balance of phytoplankton biomass fluctuated after June, no significant changes were seen until December. Therefore, the risk of a decrease in oyster food was thought to increase after June. The mass balance of phytoplankton biomass in both low (360 ropes × 25masters × 10ind./master) and high (400 ropes × 30 masters × 15ind./master) culture density (approximately 450 oyster longline facilities) was always >0 after the tsunami. The number of longline facilities before the 2011 tsunami (approximately 1,100) did not negatively impact the oyster food supply if culture density was low. However the mass balance of phytoplankton biomass under high culture density before the tsunami was calculated as negative from June to August and from October to November. We speculate that an increase in the number of longline facilities and high-density culture would result in a decrease in oyster food. Food availability under low culture density before the tsunami (1,118 longline facilities × 360 ropes × 25 masters × 10 ind./master) was the most suitable, because the mass balance of phytoplankton biomass was >0, and oyster density was the highest of the four conditions.

The microalga Nannochloropsis oculata is used as a diet for rotifers and can enrich the highly unsaturated fatty acid (HUFA) proportion of rotifer polar lipids (PL-HUFA). For efficient enrichment of PL-HUFAs in rotifers, we evaluated nutrient–sufficient or –deficient cell populations to clarify when the alga should be harvested and fed to rotifers. The nutrient conditions for N. oculata were spectrophotometrically monitored during cultivation and cells with nutrient sufficiency (NS) and phosphorous deficiency (PD) were harvested. The PD cells exhibited reduced chlorophyll a content, photosynthetic activity, and growth rate and accumulated total lipids as non-polar lipids (NLs). A decrease in the proportion of HUFA to total lipids between two nutrient states corresponded to a similar phenomenon observed in NLs. On the other hand, PLs, including glycolipids and phospholipids, showed different trends. Glycolipids did not change fatty acid composition between two states. Phospholipids, however, showed significantly higher contents of arachidonic acid (ArA) and eicosapentaenoic acid (EPA) only in the early periods of PD culture. It was concluded that phosphorous deficiency stimulated cells to increase the fatty acid desaturation rate of non-plastidial membranes. Mitochondria in the PD cells decreased in number but increased in size and mass. Such adaptation of mitochondria can be associated with high desaturation of non-plastidial membranes. When the early P–limited phase culture was used for the enrichment of rotifers, PL-ArA and EPA of the rotifers were enhanced by twice as much as those fed on NS cells. This study provides evidence that the beginning of phosphorous deficiency is the optimum time to harvest N. oculata cells for enhancing rotifer PL-HUFAs.

We calculated the mass balance of major congeners of dioxins derived from chloronitrophen (CNP) and pentachlorophenol (PCP) found in Sendai Bay, in order to characterize the present status of marine pollution caused by dioxins and enable the establishment of appropriate countermeasures against dioxin contamination. According to published statistics, about 58 000 t of CNP and about 22 000 t of PCP were shipped to Miyagi Prefecture over a 40-year period, and based on the these amounts of CNP and PCP, we estimated that 30.7 t of 1,3,6,8-tetrachlorinated dibenzo-p-dioxin (1,3,6,8-TeCDD), 1,3,7,9-TeCDD, and octa-chlorodibenzo-p-dioxin (OCDD) were introduced into the terrestrial environment as impurities contained in both pesticides. Mass balance analysis results show that most of these dioxins remained in the terrestrial environment and were not transported by runoff into Sendai Bay. Moreover, degradation mainly reduced the amount of dioxins in the terrestrial environment, instead of runoff or volatilization. Although large amounts of CNP and PCP were shipped to Miyagi Prefecture, only 0.8% of the total quantity of 1,3,6,8-TeCDD, 1,3,7,9-TeCDD, and OCDD contained in pesticides that were applied to paddy fields reached Sendai Bay via the discharge of major rivers. Moreover, most dioxins transported to the bay either flowed offshore or settled at the bottom of the bay. And there was very little bioaccumulation in marine organisms, particularly commercially valuable species.

The study was performed to evaluate the percutaneous penetration of ketoprofen after transdermal administration using a microdialysis technique in pigs, in comparison with rats. Ketoprofen release from patches was determined by analysis of the remaining drug content after application to hairless rats and pigs. Skin and knee joint penetration of ketoprofen was tested by microdialysis, and recovery was determined by retrodialysis. Residual rates in hairless rats and pigs were 68.1 ± 1.6% and 81.7 ± 4.4%, respectively, at 10h. The average recoveries of ketoprofen over 480 min in the skin and knee joint cases were 72.0 ± 3.4% and 9.8 ± 6.2% in rats and 72.3 ± 2.5% and 57.6 ± 3.1% in pigs, respectively. In rats, ketoprofen was rapidly absorbed with transdermal administration, with C(max) values of 191.7 ± 76.2 and 35.5 ± 21.7 ng/mL and AUC(0-8h) values of 918.2 ± 577.5 and 195.9 ± 137.1 ngh/mL, respectively, for the skin and knee joint. The C(max) values for the pig were 20.9 ± 18.5 and 3.7 ± 3.0 ng/mL, with AUC(0-8h) values of 73.1 ± 69.2 and 16.1 ± 16.1 ngh/mL. Ketoprofen concentrations within skin and knee joint of non-application sites in rats and pigs were less than 0.8 ng/mL. Transdermal administration of ketoprofen significantly reduced prostaglandin E2 levels in the skin of the application site and showed a tendency for inhibition in the knee joint. We thus demonstrated that topical patches containing ketoprofen can deliver the drug through the skin and knee joint of pigs and rats via direct diffusion, and microdialysis data with the pig may be useful for the prediction of human tissue penetration of drugs with transdermal administration.

The mechanisms by which mitogen-activated protein kinases (MAPK) respond to the input of UV-induced signal transduction pathways and the resulting biological functions are not well understood. We investigated whether the level of oxygen tension of culture was responsible for the differential activation of MAPK and different cellular outcomes in UVC-irradiated cells. The intracellular oxidative level of normal human fibroblast-like cells in a normal atmosphere (normoxic, 20% O2) was increased within 30 min after UVC irradiation. When cells were cultured at lower oxygen tension in the presence of an antioxidant N-acetyl-L-cysteine (NAC) or under physiologically hypoxic (5% O2) conditions, the elevation of the oxidative level by UV-irradiation was significantly reduced. Among MAPK, extracellular-signal related kinase (ERK) 1/2 was activated by UV regardless of the oxidative level, while c-Jun N-terminal kinase (JNK) activation was inhibited in NAC-treated and in hypoxic cultures. In addition, in cultures at lower oxygen tension, there was less apoptosis and cell survival was enhanced. These results suggest that UV-induced oxidative stress was responsible for intracellular signaling through the JNK pathway. Furthermore, the balance between ERK1/2 and JNK activities after UV irradiation under different oxygen tensions possibly modified cellular outcome in response to UV.

We investigated the changes in phytoplankton quantity and diversity after the March 11, 2011, Tohoku earthquake and tsunami in Ofunato Bay and in the mouth of Kesennuma Bay in northeastern Japan. Phytoplankton quantities increased in Ofunato Bay, and diversity changed. The phytoplankton assemblages other than diatoms increased near the water surface after the earthquake. In contrast, a clear change was not observed at Iwaisaki, at the mouth of Kesennuma Bay, during the survey. These results suggest that the influence of the tsunami on phytoplankton varied by location. In this study, phytoplankton in Ofunato Bay were affected by the tsunami, which is enclosed and was easily affected by the terrestrial environment and broken seawall. Limited changes were observed at Iwaisaki at the entrance to Kesennuma Bay.

Radiotherapy for malignant pelvic disease is often followed by acute radiation colitis (ARC). It has been reported that sucralfate treatment has a protective effect against ARC, though the mechanisms of action are unknown. The effects of sucralfate on X-ray radiation-induced apoptosis was studied at 4 Gy in the colonic crypt cells of rats. Sucralfate enemas given prior to radiation resulted in the following: (1) reduction in number of apoptotic colonic crypt cells; (2) reduction in number of caspase-3 positive cells; (3) decreases in p53 accumulation and p21 expression; (4) decreases of Bax/Bcl-2 ratio. The protective effects of sucralfate against ARC may be partially due to the suppression of radiation-induced apoptosis by way of p53 in the colon and the protection of the colonic epithelial stem cell region., Journal of radiation research. 2006, 47(1), p.1-8

Quantification of lipophilic toxins in bivalves associated with diarrhetic shellfish poisoning was investigated by liquid chromatography-mass spectrometry (LC-MS). Using a C8-silica reversed phase column and a mobile phase of aqueous acetonitrile containing 2 mM ammonium formate and 50 mM formic acid, okadaic acid, dinophysistoxin-1, 7-O-palmitoyldinophysistoxin-1, pectenotoxin-1, pectenotoxin-2, pectenotoxin-6, pectenotoxin-2 seco-acid, yessotoxin, and 45-hydroxyyessotoxin in bivalves were quantified by LC-MS in the negative mode. When the crude 90% methanol extracts were analyzed by LC-MS, there were no significant effects from bivalve matrices on the quantification of toxins. More than 200 bivalve samples collected from various production areas in Japan were analyzed by LC-MS. Pectenotoxin-6 and dinophysistoxin-1 were the dominant toxins in scallops and mussels, respectively. Yessotoxin and 45-hydroxyyessotoxin were also detected in both species. Comparison of the quantitative results obtained for these bivalve samples between LC-MS and mouse bioassay indicates that LC-MS is suitable for routine monitoring of lipophilic toxins in Japanese bivalves.

To understand the current situation of internal radiation exposure in the population around the Chernobyl Nuclear Power Plant (CNPP), we examined the 137Cs body burden in six residents of Belarus, Ukraine and Russia in 2002 and 2004 using the whole-body counter (WBC) at Nagasaki University (Japan). The data were compared with those of our previous study performed in 1993-1994 using the same method. In 2002 and 2004, peaks of 137Cs were detected in two residents from Gomel, which was heavily contaminated by the CNPP accident, one from Minsk (Belarus) and one from Kiev (Ukraine), but another resident from Minsk showed no 137Cs peaks. The results of the present study suggests that residents around the CNPP are still exposed to chronic 137Cs internal irradiation, probably due to the daily consumption of contaminated domestic foods, but the risk of any disease by the irradiation is quite low. Long-term follow-up of WBC around the CNPP is useful and may contribute to radiation safety regulation together with a reduction of unnecessary radiophobia for the residents.

In Sendai Bay, Japan, the total PCDD, PCDF, and Co-PCB (dioxins) concentrations in phytoplankton were equivalent to 150, 12, and 51 pg/g wet weight (ww), respectively. The average concentrations in seaweed were 3, 0.095, and 2.1 pg/g ww, respectively. The total concentrations in phytoplankton were much higher than those in seaweed, even though both groups are algae. The concentrations in zooplankton were 11, 1.1, and 110 pg/g ww, respectively. The total PCDD/F concentrations in zooplankton (primary consumers and lower-trophic-level invertebrates) were lower than in phytoplankton (primary producers), but the total Co-PCB concentration in zooplankton was higher than that in phytoplankton. The concentrations in mysids (secondary consumers and higher-trophic-level invertebrates) were 190, 18, and 290 pg/g ww, respectively. The average concentrations in shrimp (secondary consumers and higher-trophic-level invertebrates) were 120, 17, and 410 pg/g ww, respectively. The concentrations in higher-tropic-level invertebrates were higher than those in lower-trophic-level invertebrates. The average concentrations in sand lance were 4.5, 1.7, and 550 pg/g ww, respectively. The total PCDD concentration in sand lance was lower than that in zooplankton (prey of sand lance), but the total Co-PCB concentration in sand lance was higher than that in zooplankton. The bioaccumulation of PCDD congeners in sand lance differed from that of Co-PCB congeners. The bioaccumulation of PCDD/Fs from lower- to higher-trophic-level invertebrates through the food web differed from that from lower-trophic-level invertebrates to fish.

Mutation of the p53 gene is the most common genetic alteration observed in human cancers. It has been widely reported that cells with mutant p53 change radiation sensitivity. The specific mutations were not discussed in these reports. Radiation sensitivity may depend on the position of mutation of p53. We had examined four mutants of p53 (123A, 143A, 175H, and 273H) for radiation sensitivity and found that the radiation sensitivity differed. These mutant cells responded differently to accumulation of p53, induction of Bax, and apoptosis by radiation. We conclude that the response to radiation of the cells is different in the position of p53 mutation and that the radiation sensitivity depends on the position of the p53 mutation.

Objective : The aim of the study was to determine whether a β 2 -adrenoceptor agonist, formoterol, inhibits premature delivery in connection with change in estradiol and progesterone concentrations in the amniotic fluid in ovariectomized rats. Study design : Pregnant rats at the 15th day of gestation were bilaterally ovariectomized and given injection of 17β-estradiol immediately after the operation and every 24 h. An osmotic pump filled with a solution of formoterol or saline was also implanted subcutaneously into the back of each. The animals were killed by decapitation under light ether anesthesia 18, 36, 54 or 72 h after ovariectomy, and the numbers of undelivered fetuses and newborn were counted. Amniotic fluid was collected 16, 36, and 54 h after ovariectomy. Results : Formoterol (0.15 mg/(kg h)) reversed the decline in premature delivered fetuses due to 17β-estradiol 54 and 72 h after ovariectomy. Although no influence was evident regarding the progesterone and estradiol concentrations in amniotic fluid in ovariectomized rats supplemented with 17β-estradiol, formoterol significantly inhibited the increment in the estradiol/progesterone ratio as well as the elevation in prostaglandin F2α concentration. Conclusion : These findings indicate that tocolytic effects of formoterol may be associated with suppression of uterine activity due to modulation of hormone secretion.

Expression of heat shock protein 70, induced by an antiulcer drug, provides protection against gastric ulcers. However, the mechanisms responsible for this protection are not known. The expression in ulcer-resistant, spontaneously hypertensive rats was 2.8-fold higher than in normotensive rats. One hour after restraint and water immersion stress, strong nuclear immunoreactivity was observed in nuclei of surface epithelial cells at the crest of gastric mucosal folds, the first site of ulceration, only in spontaneously hypertensive rats. Heat shock cognate protein 70, which is expressed in mucus-secreting cells, was not overexpressed in spontaneously hypertensive rats. Heat shock protein 70 expression was attenuated by chemical sympathectomy, which also resulted in abolition of the increase of mucosal blood flow and aggravation of ulcers. Our results indicate that overexpression of heat shock protein 70 in the stomach seems to protect against gastric ulcers through its cytoprotective effects on gastric mucosa by increasing mucosal blood flow.

To determine the possible effect of hypergravity to modify the signal transduction of ionizing radiation, we analyzed the accumulation of p53 and the expression of p53-dependent genes, Waf-1 and Bax, using the western blot analysis. Hypergravity (20 × g) induced the accumulation of p53 in the human glioblastoma cell line A172 after 3 h of incubation. Low-dose (0.5 Gy) irradiation to the cells accumulated p53 1.5 h after irradiation, and induced Waf-1 and Bax. Under the condition of hypergravity (20 × g), the peak of p53 accumulation was shifted from 1.5 h to 3 h after irradiation, and the inductions of Waf-1 and Bax were suppressed entirely. These results indicate that hypergravity modifies the signal transduction of ionizing radiation through p53 in the cells., Journal of radiation research. 2002, 43(Supplement), p.261-264

Wortmannin is an inhibitor of PI3-kinase and acts on cultured cells at doses below 1 μM. Wortmannin also inhibits the PI3-kinase family such as ATM or DNA-PK at doses above 10 μM. There are many reports on the enhancement of cell radiosensitivity by using a high dose of wortmannin inhibiting the proteins of the PI3-kinase family. However, there have been no reports of the effects on the radiosensitivity of low doses of wortmannin inhibiting PI3-kinase. We found that low doses of wortmannin reduced the radiosensitivity of human glioblastoma cells, which had wild-type p53 . A low dose of wortmannin did not affect the accumulation of p53 and the phosphorylation of p53 at ser-15; however, a low dose reduced the induction of Waf-1 and enhanced the induction of GADD45. As the fraction of G2/M cells was reduced, however, the fraction of G1 cells was increased by a low dose of wortmannin after X-ray irradiation.

60 Co / Specific activity / Atomic bomb / DS86 / Neutrons Residual 60 Co activity in five steel samples induced by neutrons from the Nagasaki atomic bomb has been measured within about 1000 m from the hypocenter. The chemical separation of cobalt and nickel from steel samples was performed, and cobalt-enriched samples were prepared for all samples. Gamma-ray measurements were carried out with a low-background well-type germanium detector. The gamma-ray spectra for five samples were compared with the spectrum of a control sample to ensure that the observed 60 Co was actually induced by A-bomb neutrons. The activation of cobalt by environmental neutrons was also investigated. It has been shown that the present 60 Co data are consistent with earlier Hashizume’s data.

From the role of double strand DNA dependent protein kinase (DNA-PKcs) activity of non-homologous end joining (NHEJ) repair for DNA double strand breaks (DSBs), we aim to define possible associations between thermo-sensitisation and the enzyme activities in X-ray irradiated cells.DNA-PKcs deficient mouse, Chinese hamster and human cultured cells were compared to the parental wild-type cells. The radiosensitivities, the number of DSBs and DNA-PKcs activities after heat-treatment were measured.Both DNA-PKcs deficient cells and the wild-type cells showed increased radiosensitivities after heat-treatment. The wild-type cells have two repair processes; fast repair and slow repair. In contrast, DNA-PKcs deficient cells have only the slow repair process. The fast repair component apparently disappeared by heat-treatment in the wild-type cells. In both cell types, additional heat exposure enhanced radiosensitivities. Although DNA-PKcs activity was depressed by heat, the inactivated DNA-PKcs activity recovered during an incubation at 37 °C. DSB repair efficiency was dependent on the reactivation of DNA-PKcs activity.It was suggested that NHEJ is the major process used to repair X-ray-induced DSBs and utilises DNA-PKcs activity, but homologous recombination repair provides additional secondary levels of DSB repair. The thermo-sensitisation in X-ray-irradiated cells depends on the inhibition of NHEJ repair through the depression of DNA-PKcs activities.

Naupliar copepods were distributed at similar concentrations over the waters inshore and offshore of the Kuroshio Current off central Japan in early spring 1993 and 1994, overlapping with the distribution of early feeding larvae of Sardinops melanostictus. Although N, P, Si and chlorophyll a concentrations were higher in the waters inshore of the Kuroshio axis than in the offshore waters, the mean concentrations of nauplii were not statistically different between the two waters. Food availability for larval S. melanostictus did not seem to be different between the two waters in terms of the mean food concentrations. Using the critical food concentration (>9 nauplii L–1) for 25% survival during 3 days after first feeding derived from a rearing experiment, percentages in number of stations or water samples with nauplii concentrations >9 nauplii L–1 were higher in the inshore waters than in the offshore waters in both years examined. Considering that fish larvae may depend on small-scale patchiness of food for their survival, the inshore waters seemed to be more favourable for first-feeding larvae than the offshore waters.

We have constructed an in vitro system to examine how p53 mutants affect radiosensitivity. Mutations of p53 were made using in vitro mutagenesis, and mutant cDNAs were introduced into the human osteosarcoma cell line, Saos-2, which is devoid of endogenous p53. For wild type p5 both the expression plasmid and a regulation plasmid (LacSwitch system) were transfected into the cells. The radiosensitivities of clones of mutant p53 and wild type p53 were examined. Transformants of wild type p53 had increased radiosensitivity. The induction of wild type p53 protein by addition of IPTG did not significantly increase radiosensitivity. A mutation at codon 123 also increased radiosensitivity. Mutations at codons 143, 175, and 273 did not alter radiosensitivity., Journal of radiation research. 1998, 39(2), p.111-118

To elucidate the effect of ionizing radiation on the membrane anchored signal transduction, the binding of 125 I epidermal growth factor (EGF) to its receptor (EGF-R) and the EGF-dependent EGF-R tyrosine phosphorylation were examined in a human squamous cell carcinoma cell line, A431. The significant suppression of 125 I EGF binding to A431 cells was observed from 3–5 h after 10 Gy irradiation, whereas this inhibition was not observed both in nonirradiated and in 5 Gy-irradiated cells. This phenomenon was mediated by the protein kinase C pathway, because the inhibition was not observed in cells which had been pretreated with phorbol ester and treated with an inhibitor of the enzyme, H7. Scatchard analysis showed that the receptor affinity was decreased. In contrast, the level of EGF-dependent EGF-R-tyrosine phosphorylation was not decreased, compared with non-irradiated cells. These results suggest that ionizing radiation may modulate the function of EGF/EGF-R interaction through the direct activation of protein kinase C.

The associations between occupational irradiation, cigarette smoking, alcohol drinking and clinical examination data were investigated in Japanese male radiology technicians. The number of investigated examination items was 35, including 29 biochemical serum test, four hematological tests and systolic and diastolic blood pressure. The associations with each factor were evaluated using the multiple linear regression model. As single factors, radiation associated with urea nitrogen, alkaline phosphatase, monoamine oxidase and leukocyte count (four items), smoking associated with albumin-globulin index, zinc sulfate turbidity test, urea nitrogen, creatinine, neutral fat, amylase, serum iron, leukocyte count, hemoglobin and hematocrit (10 items), and drinking associated with creatinine, uric acid, glutamate oxaloacetate transaminase, leucine aminopeptidase, alkaline phosphatase and erythrocyte count (six items). As synergistic factors, the combination of radiation and smoking associated with nine items, radiation and drinking 10 items, smoking and drinking four items, and radiation, smoking and drinking two items. These results suggested that the number of items which radiation associated as single-factor were less than that of smoking and of drinking, however suggested that associations between radiation and examination data was synergistic when combined with smoking or drinking. J Epidemiol, 1995; 5 : 51-57.

The DNA double strand breaks (DSBs) induced by X ray and carbon ion beam irradiation in scid cells were analysed using pulsed-field gel electrophoresis. Scid cells and hybrid cells were ideal to study the DNA DSB repair mechanisms, because their genetic backgrounds were identical except DNA-PK activity. Induction of DNA DSBs was determined after exposure to X rays and carbon beams. DNA DSB repair was by biphasic kinetics with a fast and a slow component. For scid cells only a slow component was observed, whereas the kinetics of DSBs repair was biphasic with a fast and a slow component. It was concluded from the experimental data that the induced DSB rejoining in scid cells was due to the lack of DNA-PK activity.

The murine severe combined immunodeficient mutation (scid) is characterized by a lack of both B and T cells, due to a defect in lymphoid variable-(diversity)-joining (V(D)J) rearrangement. Scid cells are highly sensitive to both radiation-induced killing and chromosomal aberrations. Significantly reduced D0 and n values were demonstrated in scid cells and were similar to ataxia-telangiectasia (AT) cells (a unique human disease conferring whole body radiosensitivity). However, the kinetics of DNA synthesis after irradiation were different between the two cell types. In contrast with the radioresistant DNA synthesis of AT cells, DNA synthesis of scid cells was markedly inhibited after irradiation. The existence of different mutations was also supported by evidence of complementation in somatic cell hybrids between scid cells and AT cells. Our results indicate that the radiobiological character of scid is similar to AT but is presumably caused by different mechanisms.

The dose-rate effect of 252-californium neutrons was investigated using confluent cultures of mouse m5S cells. The relative biological effectiveness (RBE) of neutrons for oncogenic transformation was increased from 3.3 to 5.1 when the dose-rate was reduced from 1.8 to 0.12 cGy/min. Similarly, neutron RBE values for HPRT- mutation were 4.9 and 7.4 at dose-rates of 1.8 and 0.12 cGy/min, respectively. The increases in RBE as dose-rate was reduced were due mainly to diminished transformation- and mutation-induction by gamma-rays (the standard radiation). The yields of neutron-induced oncogenic transformation as well as neutron-induced mutation were constant for both dose rates. Our observation contrasts with reports by others using proliferating cells where both oncogenic transformation and mutation were enhanced with neutron exposure at a reduced dose-rate, the so-called inverse dose-rate effect. Since m5S cells are sensitive to postconfluent inhibition of cell division, this observation could be ascribed to cell growth conditions used in these experiments. The mechanism of the inverse dose-rate effect of neutrons suggests that the enhancement of neutron-induced mutation and oncogenic transformation at a reduced dose-rate is strongly associated with cell proliferation during exposure.

The androgen receptor (AR) is the main therapeutic target for treatment of metastatic prostate cancers. The present study demonstrates that the topoisomerase I inhibitor camptothecin selectively inhibits androgen-responsive growth of prostate cancer cells. Camptothecin strikingly inhibited mutated and wild-type AR protein expression in LNCaP and PC-3/AR cells. This inhibition coincided with decreased androgen-mediated AR phosphorylation at Ser 81 and reduced androgen-mediated AR transcriptional activity in a dose-dependent manner. Additionally, camptothecin disrupted the association between AR and heat shock protein 90 and impeded binding of the synthetic androgen [ 3 H]R1881 to AR in LNCaP cells. Camptothecin also blocked androgen-induced AR nuclear translocation, leading to downregulation of the AR target gene PSA. In addition to decreasing the intracellular and secreted prostate-specific antigen (PSA) levels, camptothecin markedly inhibited androgen-stimulated PSA promoter activity. Collectively, our data reveal that camptothecin not only serves as a traditional genotoxic agent but, by virtue of its ability to target and disrupt AR, may also be a novel candidate for the treatment of prostate cancer.

We studied X-ray-induced chromosome aberrations in ataxia telangiectasia (AT) cells containing an introduced chromosome 11 or 12 derived from normal human fibroblasts. We used microcell-mediated chromosome transfer to introduce the normal chromosomes into AT cells belonging to complementation groud D. Cells were irradiated with 1 Gy of X-rays in the G2 phase. All 5 hybrid clones with an introduced chromosome 11 showed a reduction in the frequency of chromatid-type aberrations to normal levels, whereas all 4 hybrid clones with an introduced chromosome 12 failed to show this reduction. This finding, taken together with our previous report that chromosome 11 can restore radioresistant cell killing in AT cells, indicates that a defective gene on chromosome 11 in AT cells is responsible for the hypersensitivity to not only cell killing but also chromosome aberrations. Our results suggest that a putative AT gene on chromosome 11 plays an important role in the repair process of radiation-induced DNA damage that leads to chromosome aberrations.

The structure of the linkage region of chondroitin sulfate chains attached to the hybrid proteoglycans of the Engelbreth-Holm-Swarm mouse tumor was investigated. The peptidoglycan fraction which contains oversulfated chondroitin sulfate rich in the GlcA beta 1-3GalNAc-4,6-diO-sulfate unit and undersulfated heparan sulfate rich in GlcA beta 1-4GlcNAc and GlcA beta 1-4GlcN-2N-sulfate units was isolated after exhaustive protease digestion of the acetone powder of the tumor tissue, (GlcA, glucuronic acid; GalNAc, 2-deoxy-2-N-acetylamino-D-galactose). Glycosaminoglycans were released by beta-elimination using NaB3H4 and digested with chondroitinase ABC. The linkage region fraction was separated from heparan sulfate by gel filtration and fractionated by HPLC on an amine-bound silica column. Six radiolabeled compounds (L1-L6) were obtained and structurally analyzed by cochromatography with authentic hexasaccharide alditols recently isolated by us from the linkage region, and by digestion using chondroitinase ACII, alkaline phosphatase and beta-galactosidase in conjugation with HPLC. These compounds shared the conventional hexasaccharide backbone structure: delta GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl-ol, (delta GlcA, delta 4.5-GlcA or D-gluco-4-enepyranosyluronic acid). L1 was not sulfated or phosphorylated. L2 and L4 were monosulfated at C-6 and C-4 of the GalNAc residue, respectively. Upon alkaline phosphatase digestion, L3, L5 and L6 were converted to L1, L2 and L4, respectively. Analysis of the periodate oxidation products indicated that the phosphate group in L3, L5 and L6 is located at C-2 of Xyl-ol. These results suggest that Xyl-2-O-phosphate is associated with both 4-O-sulfated and 6-O-sulfated GalNAc units and does not directly determine the sulfation pattern of chondroitin sulfate.

パーソナルコンピュータによる非密封放射性同位元素 (RI) の管理に伴うデータ処理システムを新しく開発作成した。RI取扱者の報告書に基づき, 個々のデータを入力するのみで, RIの受け入れ, 保管, 使用, 廃棄等の帳簿の作成, RIの受け入れ数量, 貯蔵数量, 使用数量などの集計が自動的に行える。管理業務の能率が上がるだけでなく, 購入や譲受から廃棄あるいは譲渡にいたるRIの流れが把握しやすくなり, 安全管理に役立てることができるようにした。