Biomedical subjects

S Asami

Publications and source records attributed to S Asami.

At least 19 recordsLinked to original sources

PubMed2001

Relationships between perceived workload, stress and oxidative DNA damage.

OBJECTIVES: The present study was performed to investigate the relationship between work-related factors, including psychological stress, and the formation of a type of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OH-dG), in order to examine their possible risk factor for occupational carcinogenesis. METHODS: A total of 54 healthy workers (27 male and 27 female, aged 41.2 +/- 12.5 years) in a company were investigated for 8-OH-dG levels in the peripheral blood leukocytes at the time of a questionnaire survey regarding several factors, such as working hours, workload, fatigue, sleep, psychological stress and the prospect of alleviating it. Subjects were limited to non-smoking and non-drinking workers to exclude the influence of cigarette smoking and alcohol drinking, which have been reported to have associations with the formation of 8-OH-dG. RESULTS: The levels of 8-OH-dG in female subjects were significantly related to the perceived workload (F = 5.56, P = 0.010), the perceived psychological stress (F = 6.15, P = 0.007), and the impossibility of alleviating stress (F = 3.82, P = 0.048). No associations were observed in male subjects. CONCLUSIONS: Psychological stress and perceived over-work appear to be related to the pathogenesis of cancer via the formation of 8-OH-dG, particularly in female workers.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

Psychosocial factors as a potential trigger of oxidative DNA damage in human leukocytes.

Although numerous studies have been carried out on the stress-cancer linkage, the results are still inconclusive. One of the useful, but rarely applied, methods to assess this linkage is to examine the relationship between psychosocial stress and cancer-predisposing genetic alterations simultaneously. We investigated whether various psychosocial factors can be associated with the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of cancer-related oxidative DNA damage, in peripheral blood leukocytes in 362 healthy workers (276 males and 86 females). After adjustments for age, body mass index, cigarette smoking, and alcohol use, female subjects showed positive relationships between the amount of 8-OH-dG and the Tension-Anxiety, Depression-Rejection, Anger-Hostility, Fatigue, and Confusion scores of the Profile of Mood States, respectively. The levels of 8-OH-dG also increased reliably in the female subjects who had poor stress-coping behaviors, particularly wishful thinking strategy, in the NIOSH general job stress instrument. There were positive relationships of the 8-OH-dG levels to average working hours, a self-blame coping strategy, and recent loss of a close family member in male subjects. These findings in a nonclinical sample of healthy adults not only provide evidence of a stress-cancer linkage, but also suggest possible sex differences in the mechanisms of stress-related cancer initiation.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

Sequence specificity of the 8-hydroxyguanine repair activity in rat organs.

The base excision repair system for 8-hydroxyguanine (8-OH-Gua) is believed to play a role in the prevention of mutations, such as GC-to-TA transversion, which leads to cancer development. However, the exact repair mechanism is still unclear. In this study, we examine whether the repair activity level for 8-hydroxyguanine, one of the major forms of oxidative DNA damage, depends on the sequence of the substrate DNA. We prepared six different oligonucleotides containing 8-hydroxyguanine as substrates and reacted them with crude extracts from the livers and kidneys of 8-week-old Sprague-Dawley rats. As a result, up to a 10-fold difference in the repair activity levels was observed, depending on the substrates used. Based on this observation, we suggest that the repair systems may act with sequence specificity on the damaged DNA.

Animals↗

PubMed2001

[Evaluation of intra-arterial infusion chemotherapy for liver metastases and lymph node metastases from gastric cancer--comparative analysis for intra-arterial group and non-intra-arterial group].

We evaluated the effects of intra-arterial infusion chemotherapy for liver metastases and lymph node metastases of gastric cancer. Of 410 patients undergoing gastrectomy in our department from July 1993 to December 2000, 29 (7.1%) had liver metastases. Intra-arterial infusion chemotherapy was carried out for 15 patients with liver metastases and 10 patients with lymph node metastases. There were 11 patients with liver metastases evaluated as follows: PR 5, NC 2, PD 4. Two patients with lymph node metastases were PR. In a comparison between the intra-arterial and non-intra-arterial chemotherapy group, it was observed among the patients with synchronous liver metastases that the survival period of the intra-arterial group was significantly longer than that of the non-intra-arterial group (p = 0.0164 logrank test). On the supposition that the survival period is counted from the day of computed tomography metachronous liver metastases was detected, in all liver metastases patients, the survival period of the intra-arterial group was significantly longer (p = 0.0212 logrank test). These results showed that the intra-arterial infusion chemotherapy is a useful treatment for gastric cancer patients with liver metastases.

Angiotensin II↗

PubMed2000

Classical conditioning of oxidative DNA damage in rats.

This study investigated whether the formation of 8-hydroxydeoxyguanosine (8-OH-dG), a known oxidative DNA modification relevant to carcinogenicity, can be classically conditioned to a novel taste in order to clarify the possible role of the central nervous system (CNS) or psychological stress on cancer initiation via a classical conditioning mechanism. Male Wistar rats underwent one or two conditioned taste aversion (CTA) experiments in which ferric nitrilotriacetate (Fe-NTA), which has renal toxicity and can induce renal cell carcinoma, served as a visceral unconditioned stimulus (US), and a saccharin solution (SAC) was used as a conditioned stimulus (CS). The 8-OH-dG levels in the group conditioned with the combination of SAC and Fe-NTA significantly increased as compared to those of the uncombined groups by two repeats of the conditioning procedure (P=0.013). The rats that showed a painful response at the Fe-NTA administration had significantly higher values of 8-OH-dG than those without pain (P=0. 003). These results not only provide the first evidence regarding classical conditioning of oxidative DNA damage using the CTA procedure, but also suggest the involvement of the CNS and psychological stress in the pathogenesis of cancer via oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2000

Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells.

Bone morphogenetic protein (BMP)-2, a member of the BMP family, plays an important role in osteoblast differentiation and bone formation. To discover small molecules that induce BMP-2, a luciferase reporter vector containing the 5'-flanking promoter region of the human BMP-2 gene was constructed and transfected into human osteosarcoma (HOS) cells. By the screening of an in-house natural product library with stably transfected HOS cells, a fungal metabolite, compactin, known as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was isolated. The stimulation of the promoter activity by compactin seemed to be specific for BMP-2 gene in HOS cells, since it had little effect on BMP-4 or SV40 promoter activity and the stimulation was not observed in Chinese hamster ovary (CHO) cells. RT-PCR analysis and alkaline phosphatase assay revealed that compactin induced an increase in the expression of BMP-2 mRNA and protein. Like compactin, simvastatin also activated the BMP-2 promoter, whereas pravastatin did not. The statin-mediated activation of BMP-2 promoter was completely inhibited by the downstream metabolite of HMG-CoA reductase, mevalonate, indicating that the activation was a result of the inhibition of the enzyme. These results suggest that statins, if they are selectively targeted to bone, have beneficial effects in the treatment of osteoporosis or bone fracture.

Anti-Bacterial Agents↗

PubMed2000

Effects of cocaine context on NAcc dopamine and behavioral activity after repeated intravenous cocaine administration.

In two conditioning experiments, identical procedures (previously shown to produce place preferences for a cocaine-paired environment) were used to assess dopaminergic and behavioral activity correlates of cocaine reward conditioning and sensitization. In these experiments, animals received repeated injections of intravenous cocaine (4.2 mg/kgx6) or saline (0.2 mlx6) on alternating days. One group in each of these experiments ('Cocaine Cues') occupied a consistent distinctive environment during cocaine treatments and testing sessions. For the other conditioned group ('Novel'), all procedures were the same, except that the last cocaine injection was administered while animals were occupying a novel environment. During day 1 and day 6 of the cocaine treatment, behavioral activity was assessed in experiment 1 and in vivo microdialysis procedures were conducted in experiment 2. Over the course of the conditioning sessions, cocaine-induced behavioral activity (locomotion and rearing) increased significantly in the Cocaine Cues group, but not in the Novel group. In addition, cocaine-induced increases in NAcc dopamine levels were significantly greater when cocaine-experienced animals were tested in a cocaine-paired environment compared to equally experienced and cocaine-naive animals tested in a novel environment. Context-dependent behavioral sensitization is a well-documented phenomenon. The observation of a corresponding enhancement of dopamine efflux in lieu of a lengthy withdrawal period is uncommon, but can be attributed to methodological differences across studies. The present study uniquely demonstrates concurrent context-dependent potentiation of behavioral and dopaminergic responses to cocaine occurring in conjunction with cocaine reward.

Animals↗

PubMed2000

Increase in 8-hydroxyguanine and its repair activity in the esophagi of rats given long-term ethanol and nutrition-deficient diet.

Epidemiological studies have shown that an increased risk of esophageal cancer is associated with the chronic consumption of alcoholic beverages, although alcohol itself is not a carcinogen in animal models. Reactive oxygen species produced by the metabolism of ethanol or by chronic inflammation may play an important role in the carcinogenic process. In this study, we analyzed one type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), and its repair activity in the esophagus as indicators of cellular oxidative stress in rats given long-term ethanol and an autoclaved diet (nutrition-deficient diet). Three-week-old male Sprague-Dawley rats were fed an ethanol beverage whose concentration was increased from 12 to 70% over 20 weeks. When the concentration reached 50%, the diet of one group was changed from the regular diet to an autoclaved diet. At the feeding periods of 20, 25, 30, and 35 weeks, the rats were sacrificed and the 8-OH-Gua levels and repair activities within the esophagi were measured. After 30 weeks of ethanol- and autoclaved diet-feeding, significant increases of 8-OH-Gua and its repair activity were observed in the esophagi, but not in those of the ethanol- and normal diet-fed rats. This result indicates that the combined effects of long-term ethanol consumption and nutritional deficiency may be involved in inducing oxidative stress in the rat esophagus.

Animals↗

PubMed2000

Relationship between renal dysfunction and bone metabolism disorder in male rats after long-term oral quantitative cadmium administration.

To investigate the importance of the cadmium (Cd) exposure condition in the evaluation of toxic effect on renal function and bone metabolism, six groups of Male Wistar rats were given Cd at respective daily doses of 2, 5, 10, 20, 30 and 60 mgCd/kg (as CdCl2) via a gastric tube for 6 consecutive days a week for 60 weeks. In the groups given a low Cd dose (2, 5 and 10 mgCd/kg), relatively more Cd accumulated in the kidney without liver damage than in the liver. In the high Cd dose groups (20, 30 and 60 mgCd/kg), on the other hand, more Cd accumulated in the liver than in the kidney. The daily intake of Cd dose from the intestinal tract in each experimental group was deduced to be about 0.36%-0.54% of the cumulative dose of oral Cd administration. The daily intake of Cd into the body was estimated as 7, 22, 40, 100, 120, 260 microgCd/kg/day in the experimental groups of 2, 5, 10, 20, 30 and 60 mgCd/kg/day, respectively. Increase of plasma enzyme activity (GOT, GPT) and of urinary enzyme excretion (NAG, AAP, GST), reflecting hepatic damage and renal dysfunction, was found in the high Cd dose groups (30 and 60 mgCd/kg) from the 5th week. Non-CdMT concentration in the kidney was also significantly high in the high Cd dose groups. In the low Cd dose groups (2 and 5 mgCd/kg), although the renal Cd concentration was higher than that of the high Cd dose groups, prominent renal dysfunction and hepatic damage were not observed. Regeneration, vacuolization, and eosinophilic bodies in proximal tubular tissue were mainly observed in the groups subjected to 20, 30 and 60 mgCd/kg administration. Very slight regeneration was also observed in the renal proximal tubular tissue at the 30th week for the 5 mgCd/kg and 10 mgCd/kg groups, and at the 60th week for the 2 mgCd/kg group. Remarkable decrease of bone mineral density at the midpoint of the femur was found in the high Cd dose groups. Also, the decrease in bone mineral density was observed before or after the manifestation of the renal dysfunction, depending on the dose and the duration of Cd administration. Urinary excretion of Pyr, DPyr, and Ca increased and plasma BGP decreased in the higher Cd dose groups. Osteoid volume in the femur tissue was not increased significantly by Cd exposure. Based on these results, it was suggested that Cd exposure caused osteoporotic change. The results of the present study suggested that the toxic effect of Cd on renal function and that on bone metabolism were caused at different times and that renal Cd concentration after long-term oral Cd administration depended on the dose and the duration of Cd exposure.

Administration, Oral↗

PubMed2000

[Complications related to arterial infusion chemotherapy in patients with hepatic metastasis from colorectal cancer].

Complications of hepatic arterial infusion chemotherapy were analyzed in 30 cases with hepatic metastasis from colorectal cancer from July 1993 to February 2000 in our department. Thirty patients were treated with three kinds of arterial infusion course that mainly consisted of 5-FU. Complications resulting in interruption of therapy occurred in 10 patients (33%), and there was no difference in the incidence rate of complications among the three chemotherapy regimens. The complications with our therapy were hepatic arterial occlusion in two patients, catheter tip dislocation in four patients, fistulus between the hepatic artery and common bile duct in two patients, and fistulus between the hepatic artery and duodenal bulb in two patients. Four patients who had severe complications with fistulus all underwent hepatectomy, especially right hepatic lobectomy in two cases. Sixty percent of our patients had complications after hepatectomy, so regular GIF and DSA are necessary to prevent severe complications after hepatectomy.

Adult↗

PubMed1999

Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos.

Asbestos and man-made-mineral fibers are known to increase one type of oxidative DNA damage, 8-hydroxyguanine (8-OH-(Gua), in vitro. In this study, we analyzed the 8-OH-Gua level in DNA and its repair activity after a single intratracheal instillation of fibers (crocidolite or glass) or saline to Syrian hamsters or Wistar rats. The 8-OH-Gua level was measured with a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) system. The 8-OH-Gua repair enzyme activity was determined with an endonuclease nicking assay using a 32P-labeled or fluorescently labeled 22mer DNA that contains 8-OH-Gua at a specific position. A significant increase in the 8-OH-Gua level in the lung DNA was observed 1 day after the exposure to crocidolite, as compared to the saline control. The repair activity was increased significantly at 7 days. On the other hand, after exposure to glass fibers, little or no increase of these carcinogenicity indicators was detected. These assays of 8-OH-Gua and its repair activity in short-term animal experiments will be useful for evaluating the carcinogenicity of fibers. This is the first report of the increase of 8-OH-Gua and its repair activity in the animal lung after the instillation of asbestos fibers.

Animals↗

PubMed1998

2-Hydroxyadenine, a mutagenic form of oxidative DNA damage, is not repaired by a glycosylase type mechanism in rat organs.

Oxygen radicals are known to play a role in causing cellular DNA damage, which is involved in carcinogenesis. 8-Hydroxyguanine (8-OH-Gua) is a major form of oxidative DNA damage and is known as a useful marker of DNA oxidation. Recently, we found another type of oxidative DNA damage, 2-hydroxyadenine (2-OH-Ade), which has a mutation frequency comparable to that of 8-OH-Gua. We compared the repair activities for two types of oxidative DNA damage, 8-OH-Gua and 2-OH-Ade, in 7-week-old male Sprague-Dawley (SD) rat organs. The repair activities were measured by an endonuclease nicking assay using 22 mer [32P]-end-labeled double-stranded DNA substrates, which contained either 8-OH-Gua (opposite C) or 2-OH-Ade (opposite T or C). In all of the SD rat organs we studied, the nicking activity for 2-OH-Ade was not detected, while that for 8-OH-Gua was clearly detected with the same conditions. Moreover, the 2-OH-Ade nicking activity was not induced in Wistar rat kidney extracts prepared after ferric nitrilotriacetate (Fe-NTA) treatment, which is known to increase 8-OH-Gua repair activity. These results suggest that 2-OH-Ade might not be repaired by the glycosylase type mechanism in mammalian cells.

Animals↗

PubMed1998

Effects of forced and spontaneous exercise on 8-hydroxydeoxyguanosine levels in rat organs.

We investigated the effects of forced and spontaneous exercise on the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a form of oxidative DNA damage, in rat organs (heart, lung, and liver). Rats were randomly assigned to one of three groups: forced exercise group (F), spontaneous exercise group (S), and sedentary control group (C). The mean levels of 8-OH-dG in the F group were 1.9-, 2.1-, and 2.4-fold higher in the heart, lung, and liver DNA, respectively, than in the S group. In the S group of rats, the distance run was not significantly correlated to the 8-OH-dG levels in the heart, lung, and liver DNA. These results demonstrate that the intensity of exercise is an important determinant in DNA damage, and suggest that spontaneous physical exercise is beneficial for maintaining a low level of oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1998

Reduction of 8-hydroxyguanine in human leukocyte DNA by physical exercise.

We investigated the effect of physical exercise on the level of 8-hydroxyguanine (8-OH-Gua), a form of oxidative DNA damage, and its repair activity in human peripheral leukocytes. Whole blood samples were collected by venipuncture from 21 healthy male volunteers (10 trained athletes and 13 untrained men), aged 19-50 years, both before and after physical exercise. Trained athletes showed a lower level of 8-OH-Gua (2.4+/-0.5/10(6) Gua, p = 0.0032) before exercise when compared to that of untrained men (6.2+/-3.5). The mean levels of 8-OH-Gua of untrained subjects decreased significantly (p = 0.0057) from 6.2+/-3.5/10(6) Gua (mean+/-SD/10(6) Gua) to 3.3+/-1.4/10(6) Gua after physical exercise. On the other hand, the mean levels of repair activity of untrained subjects significantly increased after exercise (p = 0.0093) from 0.037+/-0.024 (mean DNA cleavage ratio+/-SD) to 0.056+/-0.036. In the trained athletes 8-OH-Gua level and its repair activity were not changed before and after the exercise. We also observed inter-individual differences in 8-OH-Gua levels and its repair activities. These results suggest that physical exercise causes both rapid and long-range reduction of oxidative DNA damage in human leukocytes, with individually different efficiencies.

Adult↗

PubMed1997

Cigarette smoking induces an increase in oxidative DNA damage, 8-hydroxydeoxyguanosine, in a central site of the human lung.

To evaluate the effect of cigarette smoking on oxidative stress in lung tissues, we compared the levels of a type of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OH-dG), in tissue obtained from the central sites of lungs from 14 current smokers, seven ex-smokers and nine non-smokers. The mean level of 8-OH-dG in the lung tissues from smokers was 1.43-fold higher than that of the non-smokers (the difference was statistically significant, P = 0.0262). A positive correlation between the 8-OH-dG levels in normal lung tissues and the Brinkman index was obtained from smokers and ex-smokers (r = 0.525; P = 0.0134). A positive correlation was also obtained for the 8-OH-dG levels in normal lung tissues and the number of cigarettes smoked per day (r = 0.436; P = 0.0132). These results suggest that oxidative DNA damage is induced in lung DNA by cigarette smoking.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1996

Increase of a type of oxidative DNA damage, 8-hydroxyguanine, and its repair activity in human leukocytes by cigarette smoking.

To investigate the oxidative stress induced by cigarette smoking, the levels of a form of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), and its repair activity in the leukocytes of current smokers, ex-smokers, and complete nonsmokers were measured. The mean level of 8-OH-Gua was 1.88-fold higher in smokers as compared to complete nonsmokers (the difference was statistically significant, P = 0.013). The mean 8-OH-Gua repair activity was 1.6-fold higher in smokers than complete nonsmokers (the difference was statistically significant, P = 0.0053). A positive association was observed for the 8-OH-Gua levels and its repair activity. Considerable interindividual variations in the 8-OH-Gua levels (current smokers, 3.5-fold; nonsmokers, 7.2-fold) and in its repair activity (current smokers, 7.5-fold; nonsmokers. 5.5-fold) were observed. These results demonstrate that not only smoking status but also life-style, environment, and genetic differences might have effects on the level of 8-OH-Gua and its repair activity in human leukocytes.

Adult↗

PubMed1996

Increased 8-hydroxyguanine levels in DNA and its repair activity in rat kidney after administration of a renal carcinogen, ferric nitrilotriacetate.

The renal carcinogen, ferric nitrilotriacetate (Fe-NTA), is known to induce oxidative stress and the subsequent formation of a type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), in the rat kidney (Umemura et al., 1990). Using an improved DNA isolation method (Nakae et al., 1995), which reduces the background level of 8-OH-Gua, we found a five-fold increase in the 8-OH-Gua level in kidney DNA after a single i.p. injection of Fe-NTA. On the basis of the report that 8-OH-Gua repair activity is enhanced after cells are exposed to oxidative stress due to ionizing radiation (Bases et al., 1992), the measurement of 8-OH-Gua repair activity will also be useful to assess cellular oxidative stress. The 8-OH-Gua repair enzyme activity was determined with an endonuclease assay using a 22 mer DNA that contains 8-OH-Gua at a specific position. A five-fold increase in the 8-OH-Gua repair activity as compared with the control, was observed in the target organ, the rat kidney, 120 h after Fe-NTA administration. In the non-target organ, the liver, the increase was not as large (two-fold). This simple assay of oxidative DNA damage repair will be useful for evaluating the carcinogenicity of oxygen radical forming chemicals, in addition to chemical analyses of oxidative DNA damage.

Animals↗

PubMed1996

8-hydroxyguanine levels in nuclear DNA and its repair activity in rat organs associated with age.

8-Hydroxyguanine (8-OH-Gua) is one of the most abundant types of oxidative DNA damage. The levels of 8-OH-Gua, and its repair activity, were quantified in 3-week-, 5-month-, and 30-month-old male Sprague-Dawley rat organs such as liver, kidney, spleen, lung, small intestine, and brain. The levels of 8-OH-Gua were significantly higher in the 5-month-old rat kidney and brain and 30-month-old rat spleen when compared to that of the 3-week-old rats. However, no significant differences were found in the organs between 5- and 30-month-old rats that were due to the aging process. The repair activity levels of kidney, spleen, and lung were higher than those of liver, small intestine, and brain. This pattern was consistent for the three age stages.

Aging↗