Biomedical subjects

H Kobayashi

Publications and source records attributed to H Kobayashi.

At least 415 records · Page 23Linked to original sources

PubMed2000

Gender differences in the antidiarrheal effect of zaldaride maleate in rats.

The amelioration of secretory diarrhea has been reported after the administration of zaldaride maleate (ZAL), a selective calmodulin inhibitor, to male rodents. In this study, the antidiarrheal effect of ZAL in female rats was compared with that in male rats. In female and male rats, ZAL significantly ameliorated 16,16-dimethyl prostaglandin E2-induced diarrhea at doses of 1 and 3 mg/kg (p.o.), respectively, with ID50 values of 0.7 mg/kg (p.o.) in the females and 10.3 mg/kg (p.o.) in males. In castor oil-induced diarrhea, ZAL also significantly reduced the incidence of diarrhea in female and male rats at doses of 10 and 30 mg/kg (p.o.), respectively. When the same dose of ZAL was given orally to female and male rats, the maximum plasma level of this compound was approximately 3 times higher in female rats than in male rats. In contrast, after intravenous administration of the same dose of ZAL to female and male rats, the total clearance of this compound was similar. In an Ussing chamber experiment, the inhibitory action of ZAL on vasoactive intestinal polypeptide-induced ion secretion in the colon showed no difference between female and male rats. In conclusion, the antidiarrheal effect of ZAL in female rats is more potent than that in males, and could be due to the difference in plasma levels of this compound between female and male rats after oral administration.

16,16-Dimethylprostaglandin E2↗

PubMed2000

Comparison of the antidiarrheal effects of zaldaride maleate and its optical isomers in rats.

Zaldaride maleate (ZAL), a calmodulin inhibitor, that ameliorates secretory diarrhea in rodents, has a racemic structure. In this study, we compared the antidiarrheal and antisecretory effects of ZAL and its optical isomers, R(-)-isomer and S(+)-isomer, in rats. In Ussing chamber experiments, the inhibitory action of ZAL on acetylcholine-induced ion transport in the rat colonic mucosa was equipotent for both optical isomers, with IC50 values of approximately 3--4 micromol/l. In castor-oil-induced diarrhea, ZAL and its S(+)-isomer inhibited the incidence of diarrhea, whereas the R(-)-isomer had no effect. In 16,16-dimethyl prostaglandin E2-induced diarrhea, ZAL, the S(+)-isomer and the R(-)-isomer significantly ameliorated diarrhea at doses of 30, 10 and 30 mg/kg (p.o.), respectively; the ED50 values were 25, 10 and above 30 mg/kg (p.o.), respectively. The pharmacokinetic parameters after administration of 30 mg/kg (p.o.) of each compound were as follows: ZAL (Cmax: 378 ng/ml, AUC0-12: 1650 ng-h/ml); S(+)-isomer (Cmax: 565 ng/ml, AUC0-12: 2230 ng-h/ml) and R(-)-isomer (Cmax: 271 ng/ml, AUC0-12: 613 ng-h/ml) (mean, N=4). In conclusion, despite the fact that the antisecretory actions of ZAL and its optical isomers are the same, the antidiarrheal actions of ZAL and its S(+)-isomer are more potent than that of the R(-)-isomer. The antidiarrheal actions of ZAL and its optical isomers may be related to plasma levels.

Animals↗

PubMed2000

Relationship of two ribonucleases with molecular masses of 45 kDa and 37 kDa from the culture medium of Lentinus edodes.

Lentinus edodes (shiitake) produces three base non- specific and acid ribonucleases, RNase Le2, RNase Le37 and RNase Le45. The primary structures of the former two RNases, having molecular masses about 24 and 37 kDa, respectively, have been elucidated to be members of the RNase T2 family. The latter two are excreted from mycelia into the medium. In this report, we estimated the primary structure of RNase Le45 using the following experimental evidence. (i) The partial amino acid sequence of RNase Le45 determined that up to about 60% of total protein was identical with that of RNase Le37. (ii) The amino acid composition of RNase Le45 was identical to that of RNase Le37. (iii) The elution profiles on HPLC of lysylendopeptidase and Staphylococcus aureus V8 protease digests of RCM-RNase Le45 (reduced and S-carboxymethylated RNase Le45) were very similar to those of RNase Le37, except for the absence of C-terminus peptide which contained O-glycosylated peptides. However, RNase Le45 contained about 70 residues of mannose and 4 residues of hexosamine. These values were more than twice those of RNase Le37. (iv) RNase Le45 was immunologically indistinguishable from RNase Le37. (v) After treatment with both glycosidase EndoH and alpha-mannosidase, RNases Le37 and Le45 gave complex bands by slab-gel electrophoresis. However, one of the major bands with the highest mobility from RNase Le45 and Le37 showed the molecular mass of 29 kDa in common, which is slightly larger than that of RNase Le2 containing no carbohydrate. These results indicated that RNase Le45 is an enzyme which is a heavily glycosylated species of RNase Le37.

Amino Acid Sequence↗

PubMed2000

Isolation and characterization of bioactive metabolites from marine-derived filamentous fungi collected from tropical and sub-tropical coral reefs.

Two new compounds, paecilospirone (1) and phomopsidin (2), and seven known compounds, chaetoglobosin A (3), griseofulvin (4), fusarielin A (5), fusapyrone (6), deoxyfusapyrone (7), and verrucarins J (8) and L acetate (9), have been isolated and characterized from marine-derived fungi collected in tropical and sub-tropical coral reef environments. The utility of marine-derived fungi as a source of bioactive secondary metabolites is discussed.

Animals↗

PubMed2000

Synthesis, conformation, and chemical properties of new mini parallel double-stranded peptides conjugated with -Phe-Phe- and -Phe-Phe-X-sequences.

To investigate the chemical conformations and functions of the -Phe-Phe-Val- or -Phe-Phe- sequences contained in the Alzheimer's disease related beta-amyloid peptide, a series of mini parallel double-stranded peptides conjugated with two peptide residues to one spacer were designed and prepared. The structure of the compounds was elucidated by circular dichroism (CD) spectrum and NMR two dimensional (2D) nuclear Overhauser enhancement and exchange spectroscopy (NOESY) measurments. The structure of 1,2-ethano-bis(L-Phe-L-Phe-L-Leu), 1,12-dodecano-bis(L-Phe-L-Phe-L-Leu), 1,12-dodecano-bis(L-Phe-L-Phe-L-Val), and 1,12-dodecano (D-Phe-D-Phe-D-Leu) conjugated with L-Leu and L-Val residues show a beta-turn-like nucleation. The dihedral angles (theta = +75 degrees, omega = +180 degrees, phi = +90 degrees, phi = -87 degrees, psi = +180 degrees) obtained from experimental coupling constant (J) data, etc. support that 1,12-dodecano-bis(L-Phe-L-Phe) adopts beta-turn mimic nucleation. The 1,12-dodecano- bis(L-Leu-L-Leu-L-Phe), 1,12-dodecano-bis(L-lle-L-Phe-L-Leu), and 1,12-dodecano-bis(L-Phe-L-Val-L-Leu), etc. adopt most probably a random structure by CD studies. It was found by titration spectrum that an inclusion complex of 1:1 ratio (association constant; azobenzene (guest, Ka=1.0 x 10(4)M-1) is formed between 1,12-dodecano-bis(L.-Phe-L-Phe-L-Leu) and [L0]=1.758 x 10(-5)M-1). Moreover, the stability of the complexes was increased in order of 1,12-dodecano-bis(L-Phe-L-Phe-L-Leu) x azobenzene> 1,12-dodecano-bis(L-Phe-L-Phe-L-Val) x azobenzene> 1,12-dodecano-bis(L-Phe-L-Val-L-Leu) azobenzene. The data show that X-Phe-L-Phe-L-spacer(S)-L-Phe-L-Phe-X (X=amino acids; S = 1,2-ethano- and 1,12-dodecano-) plays an important role as a binding site of the artificial receptor. The hydrophobic interaction of the four Phes in the two strands is a very interesting issue in the physiological action of proteins as well as the conformation of the backbone of X-L-Phe-L-Phe-spacer(S)-iL-Phe-l.-Phe-X.

Amyloid beta-Peptides↗

PubMed2000

Acceleration by KW-5092 of intestinal motility associated with acetylcholine release in vivo.

Effect of KW-5092 ([1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]-2- imidazolidinylidene]propanedinitrile fumarate) on intestinal motility and release of endogenous acetylcholine (ACh) were measured simultaneously in the small intestine of anesthetized dog using the in vivo microdialysis method. Intraarterial and intravenous administrations of KW-5092 accelerated the intestinal motility and increased dialysate ACh concentrations. These KW-5092-induced responses paralleled the increase in blood concentration of KW-5092. Thus, the acceleration of intestinal motility by KW-5092 was found in vivo to be associated with an increase in ACh release from the intestinal cholinergic neurons.

Acetylcholine↗

PubMed2000

[Trends in variation within the day and between days of subjective symptoms of fatigue in adolescent males].

The purpose of this study was to clarify the trends in the variation within the day, and between days, of subjective symptoms of fatigue (SSF) in the daily life of male students. A SSF questionnaire (54 items) with guaranteed validity and reliability was administered to 104, 15-16 year-old healthy students, 3 times a day, in the morning (about 08:50), mid-day (about 12:10) and afternoon (about 16:10) for 5 days from Monday to Friday. As the main statistical analysis, two-way (day and week) ANOVA and post-hoc t tests were used. The SSF questionnaire was considered to have very high reliability because Cronbach's alpha coefficients in each survey point of time were .967-.977. SSF complaints between days were low on the whole, but complaints of drowsiness were relatively high. The trends in variation of SSF between days were greater than those within the day. The trends in variation within the day were noticeable in complaints regarding drowsiness and loss of vigor. Complaints regarding languor became high from the middle of the week to the weekend. On the other hand, SSF complaints except for languor, were high at the beginning of the week, especially on Monday and became lower after Tuesday. There is a trend in variation within the day for symptoms regarding drowsiness and loss of vigor. The trend in variation between days was confirmed for many SSFs, and was noticeable as compared to those within the day. Complaints regarding languor were high on the weekend, and SSF complaints except for languor were high at the beginning of the week, especially on Monday.

Adolescent↗

PubMed2000

[The proposal of the activities of daily living (ADL) index for institutionalized older adults].

The purpose of this study was to propose the ADL index constructed with a unidimensional scale based on item difficulty for institutionalized older adults. Six hundreds and three subjects (159 males and 444 females) were divided into the following four groups based on assisting devices for movement: G1 did not use assisting devices for movement; G2 used a stick or a walker; G3 used a wheelchair; G4 could not move. As the results of examinations from the points of the approximation of proportions, non-answer rates and agreement rates of each item according to 74 ADL items representing 9 ADL domains, the 27 ADL items were selected as utility items. The reliability and unidimensionality of the ADL index consisting of 27 items were considered to be high. As the results of examining the difficulty of items and ADL ability characteristics of each group, the ADL concerning movement and other lower limb activity in G1 and G2, and concerning changes of posture and manual activity in G3 and G4 were considered to reflect the individual differences of ADL ability, respectively. The numbers of ADL items which should first be assessed in each group were as follows: 20 items in G1; 21 items in G2; 21 items in G3; 11 items in G4.

Activities of Daily Living↗

PubMed2000

Amino acid sequence of an unique ribonuclease with a C-terminus rich in O-glycosylated serine and threonine from culture medium of Lentinus edodes.

The mushroom Lentinus edodes produces three base-non-specific and acid ribonucleases, RNases Le2, Le37, and Le45. The latter two are excreted from mycelia into the medium. The primary structure of RNase Le37, which had a molecular mass of 37 kDa, was sequenced. It was a member of the RNase T2 family, as is RNase Le2. RNase Le37 was some 30 amino acid residues longer at the C-terminal end than RNase Le2. The C-terminal region of RNase LE37 was rich in O-glycosylated serine and threonine. In fungal glucoamylases and chitinases, which hydrolyze raw-starch and chitin, respectively, have structures resembling the structure of the C-terminal of RNase Le37.

Agaricales↗

PubMed2000

Purification and characterization of aspartic proteinase from sunflower seeds.

Aspartic proteinases were purified from sunflower seed extracts by affinity chromatography on a pepstatin A-EAH Sepharose column and by Mono Q column chromatography. The final preparation contained three purified fractions. SDS-PAGE showed that one of the fractions consisted of disulfide-bonded subunits (29 and 9 kDa), and the other two fractions contained noncovalently bound subunits (29 and 9 kDa). These purified enzymes showed optimum pH for hemoglobinolytic activity at pH 3.0 and were completely inhibited by pepstatin A like other typical aspartic proteinases. Sunflower enzymes showed more restricted specificity on oxidized insulin B chain and glucagon than other aspartic proteinases. The cDNA coding for an aspartic proteinase was cloned and sequenced. The deduced amino acid sequence showed that the mature enzyme consisted of 440 amino acid residues with a molecular mass of 47,559 Da. The difference between the molecular size of purified enzymes and of the mature enzyme was due to the fact that the purified enzymes were heterodimers formed by the proteolytic processing of the mature enzyme. The derived amino acid sequence of the enzyme showed 30-78% sequence identity with that of other aspartic proteinases.

Amino Acid Sequence↗

PubMed2000

Amino acid sequence of a nuclease (nuclease Le1) from Lentinus edodes.

The fruit bodies of Lentinus edodes produce two acid nucleases, nucleases Le1 and Le3, both of which are thought to be candidates for the enzymes producing a tasty substance, 5'-GMP. To obtain the basic information on the mechanism of production of 5'-GMP, and structure-function relationship of these nucleases, the primary structure of nuclease Le1 was estimated by both protein chemistry and gene cloning. Nuclease Le1 is a glycoprotein and consists of 290 amino acid residues, and about 2 and 6 residues of hexosamine and neutral sugar, respectively. The nucleotide sequence of cDNA and genomic DNA encoding nuclease Le1 indicated the presence of 20 amino acid residues of a signal peptide. Nuclease Le1 has 115 and 108 residues of identical amino acid residues with nucleases P1 and S, respectively. The amino acid residues concerning the coordination with Zn2+ in nuclease P1 are all conserved in nuclease Le1. Nuclease Le1 contains 8 half-cystine residues and 4 of them are located at the same places as those of nucleases P1 and S.

Amino Acid Sequence↗

PubMed2000

Circulating adrenomedullin in erythrocopietin-induced hypertension.

Levels of adrenomedullin (AM) have been shown to be elevated in hypertension and chronic renal failure, suggesting that AM plays a role in the pathogenesis of these diseases. The objective of the present study was to investigate whether circulating AM is involved in erythropoietin (Epo)-induced hypertension in patients with renal anemia due to progressive renal disease. Following treatment with 6,000 IU of Epo once a week, the hematocrit (Ht) rose significantly from 25.9+/-4.0 to 33.4+/-3.3% (n=54, p<0.001) with an overall rate of increase in Ht of 0.43+/-0.04%/week. In response to treatment with Epo, a rise in mean blood pressure of >10 mmHg (Epo-induced hypertension) was found in 22% (12/54 cases) of the patients enrolled. There was no difference in the rate of Ht increase between patients with and without Epo-induced hypertension. There was a significant positive correlation between mature AM and serum creatinine (Cr) concentration before treatment with Epo. However, no correlation was found between the plasma concentration of total AM and serum Cr concentration. Long-term treatment with Epo did not influence plasma concentration of either mature AM or total AM in patients developing hypertension during the study period. These results suggest that circulating AM may play a role in the progression of renal disease. However, the present study does not support the notion that circulating AM is associated with the pathogenesis of Epo-induced hypertension. It is too early yet to claim that there is no AM-mediated mechanism in Epo-induced hypertension.

Adrenomedullin↗

PubMed2000

Decision-tree sensitivity analysis for cost-effectiveness of chest 2-fluoro-2-D-[(18)F]fluorodeoxyglucose positron emission tomography in patients with pulmonary nodules (non-small cell lung carcinoma) in Japan.

CONTEXT: Recent studies have demonstrated the potential cost-effectiveness of using 2-fluoro-2-D-[(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the management of non-small cell lung carcinoma (NSCLC), but because of differences in health-care systems, those findings may not hold true in a Japanese hospital. OBJECTIVE: To assess the cost-effectiveness of the chest CT plus chest FDG-PET strategy in Japan. DESIGN: Decision-tree sensitivity analysis based on the two competing strategies of chest CT-alone vs chest CT plus chest FDG-PET. STUDY SELECTION: A simulation of 1,000 patients in whom NSCLC, stage IIIB or less, was suspected was created using baselines of other relevant variables in regard to sensitivity, specificity, mortality, life expectancy, and cost from published data. METHODS: We surveyed the relevant literature for the choice of variables. MAIN OUTCOME MEASURES: Expected marginal cost and expected life expectancy gain for NSCLC patients. RESULTS: The chest CT plus chest FDG-PET strategy yielded an expected life expectancy gain of 0.607 years (7.3 months) per patient, compared with the alternative strategy of chest CT-alone. Using an FDG-PET examination cost of 1.0 x 10(5) yen (around $700 US) per study, the cost increment was 2.18 x 10(5) yen/yr/patient. CONCLUSIONS: The chest CT plus chest FDG-PET strategy in patients with NSCLC is unlikely to be cost-effective in Japan. However, patient life expectancy gain would increase as a result of improved staging of NSCLC. These preliminary results should be confirmed by further studies for specific environments.

Adult↗

PubMed2000

Effects of esophageal acid perfusion on airway hyperresponsiveness in patients with bronchial asthma.

STUDY OBJECTIVES: The effects of gastroesophageal reflux on airway hyperresponsiveness in patients with bronchial asthma have yet to be studied in significant detail. The purpose of the present study was to determine how esophageal acid perfusion could change airway responsiveness in patients with bronchial asthma. PATIENTS AND INTERVENTIONS: In seven patients with bronchial asthma (mean +/- SD age, 55.1 +/- 6.4 years; four women and three men), esophageal pH was monitored by a pH meter and airway responsiveness was evaluated by aerosol inhalation of methacholine, during esophageal perfusion through an esophageal tube filled with either saline solution or 0. 1N hydrochloric acid (HCl), the order of which was selected at random, in 1-week intervals. Spirometry was also performed during esophageal pH monitoring. RESULTS: A significant decrease in the geometric mean of airway sensitivity or the concentration of methacholine causing a 35% fall in respiratory conductance was observed during esophageal HCl perfusion compared with that of saline solution perfusion (p < 0.01 or p < 0.003), although no significant changes were observed in vital capacity, FEV(1), peak expiratory flow, respiratory resistance, or slope of respiratory conductance during the periods of saline solution and HCl perfusion. CONCLUSION: We concluded that an increase in airway hyperresponsiveness was induced when HCl stimulated the esophagus in patients with bronchial asthma. These results suggest that esophageal reflux is one of the important factors that aggravate asthmatic status.

Adult↗

PubMed2000

Mutation analysis of Gsalpha, adrenocorticotropin receptor and p53 genes in Japanese patients with adrenocortical neoplasms: including a case of Gsalpha mutation.

While the mechanisms of tumorigenesis for adrenocortical neoplasms remain unknown, several genes, such as Gsalpha, ACTH receptor (MC2-R), p53, and p16 tumor suppressor genes, are considered to be candidates for adrenocortical neoplasms. Mutation analysis studies have documented these genes in adrenocortical neoplasms, but these studies focused on the mutation of only one of these genes. In the present study we examined the mutations of three of these genes (Gsalpha, MC2-R, and p53) in adrenocortical neoplasms in Japanese patients. We amplified these genes using polymerase chain reaction and directly sequenced them in 30 functioning adrenocortical neoplasms. As for Gsalpha, we identified a heterogeneous substitution of glutamine to histidine at codon 227 and a gain of an Nru I restriction endonuclease site. The mutation was restricted to adenomatous tissue, and did not occur in the adjacent normal adrenal tissue or leukocytes of the patient. We did not find any mutations in MC2-R and p53. In conclusion, although the contribution of these three genes to adrenocortical tumorigenesis remains to be determined, it is suggested that the mutation of Gsalpha might play a role in functional adrenocortical neoplasms.

Adrenal Cortex Neoplasms↗

PubMed2000

Inhibitory effects of WR-2721 and cysteamine on tumor initiation in mammary glands of pregnant rats by radiation.

We evaluated the effect of WR-2721 [S-2-(3-aminopropylamino)-ethylphosphorothioic acid] and cysteamine (2-mercaptoethylamine) on the development of radiation-induced mammary tumors in rats. Pregnant rats were treated with WR-2721 or cysteamine 30 min prior to whole-body irradiation with gamma rays from a (60)Co source at a dose of 1.5 or 2.6 Gy. Additional pregnant rats were given saline and then exposed to gamma rays at a dose of 0, 1.5 or 2.6 Gy as a control. All rats were implanted with pellets of diethylstilbestrol, a tumor promoter, 1 month after termination of nursing and were observed for 1 year to detect palpable mammary tumors. No mammary tumors developed in the saline-injected nonirradiated rats. However, when rats were irradiated with 1.5 or 2. 6 Gy after saline treatment, the incidence of mammary tumors was high (71.4 and 92.3%, respectively). Administration of WR-2721 or cysteamine prior to irradiation with 1.5 Gy significantly decreased the tumor incidence (23.8 and 20.8%, respectively). Tumor prevention by either agent was less effective at the higher dose. The appearance of the first mammary tumor occurred later in rats treated with WR-2721 or cysteamine than in the control rats. An increasing rate of adenocarcinoma in the control group was observed with increasing dose from 1.5 Gy up to 2.6 Gy. However, the development of adenocarcinoma did not increase after pretreatment with WR-2721 or cysteamine in rats irradiated with 2.6 Gy. Many of the mammary tumors that developed in the control rats were of the ER(+)PgR(+) type. Administration of WR-2721 produced no tumors of the ER(+)PgR(+) type. Cysteamine treatment increased the development of ER-negative tumors. The serum concentration of progesterone was significantly higher in rats treated with WR-2721 or cysteamine than in the control rats. On the other hand, the estradiol-17beta concentration was reduced by treatment with WR-2721, but not significantly compared to the control. WR-2721 and cysteamine had no effect on the prolactin concentration of the irradiated rats. The results suggest that administration of WR-2721 or cysteamine prior to the irradiation has a potent preventive effect on theinitiation phase during mammary tumorigenesis.

Adenocarcinoma↗

PubMed2000

Toxicity and blood concentrations of xylazine and its metabolite, 2,6-dimethylaniline, in rats after single or continuous oral administrations.

To cast light on whether the carcinogenic risk of 2,6-dimethylaniline (DMA), a metabolite of xylazine, may increase by ingestion of edible tissues from domestic animals treated with xylazine, the following studies of xylazine and DMA were performed. In Experiment I, male F344 rats received a single oral administration of 150 mg/kg of xylazine hydrochloride. Rats showed symptoms suggesting loss of sensation and pain immediately after the treatment. These signs had disappeared after 3 hr, but the animals died of hydrothorax and pulmonary edema by 9 hr. The plasma concentration of xylazine was 2.88 +/- 0.95 micrograms/ml at 15 min, and then decreased to 0.10 +/- 0.01 microgram/ml at 6 hr. The plasma level of DMA remained at 0.03 to 0.04 microgram/ml during the measurement period. In Experiment II, male F344 rats were fed a diet containing 1000 ppm of xylazine hydrochloride, regarded as the maximum tolerated dose, for 4 weeks. No clear clinical signs were evident and the plasma levels of xylazine and DMA were at the detection limit (0.02 microgram/ml) or less, although follicular cell hypertrophy of the thyroid was observed in all the treated animals. In Experiment III, male F344 rats were fed a diet containing 3000 ppm or 300 ppm of DMA for 4 weeks. Histological changes, such as atrophy of Bowman's gland and irregular arrangement of olfactory epithelial cells, were only observed in the olfactory epithelium of the 3000 ppm group. The plasma levels of DMA were 0.20 to 0.36 microgram/ml in the 3000 ppm group, but under the detection limit in the 300 ppm group. These results suggest that the probability of nasal carcinogenic effects of DNA on consumers via ingestion of edible tissues from food-producing animals treated with xylazine is extremely low, since DMA levels in the blood of rats subjected to continuous administration of high doses of xylazine remained under the detection limit.

Administration, Oral↗

PubMed2000

Induction of unscheduled DNA synthesis in hairless mouse epidermis by ultraviolet light.

The activity of ultraviolet (UV) light to induce unscheduled DNA synthesis (UDS) was investigated in hairless mouse epidermis by means of an in vivo-in vitro assay using a liquid scintillation counting method. Groups of three to five 8-week-old female hairless mice were irradiated with UV-B or UV-A, then skin samples were taken and cultured individually in medium containing [3H]thymidine with or without hydroxyurea (HU) for 2 hr. DNA of the epidermis was extracted, and incorporation of [3H]thymidine and the DNA content were determined with a liquid scintillation counter and a fluorescence spectrophotometer, respectively. Induction of UDS was judged in terms of the UDS index [(the ratio of DNA synthesis in the presence of HU to that in its absence) x 100]. UV-B increased the UDS index 1 hr after irradiation of 500 J/m2, which corresponds to approximately 1 minimal erythema dose or 1 minimal edema dose, and showed a dose-dependent increase up to 17-fold in the UDS index at irradiation doses of 500 to 2,000 J/m2. In a time-course study, UV-B also increased replicative DNA synthesis (RDS) 48 hr after irradiation at 1,000 J/m2. On the other hand, UV-A did not increase the UDS index at irradiation doses of 2 x 10(5) to 8 x 10(5) J/m2. These results show that induction of UDS by UV irradiation depends on wavelength and an increase of RDS in the epidermis exposed to UV-B irradiation appears after induction of UDS.

Animals↗