Tomoko Kondo

Publications of Tomoko Kondo

• Effect of 5-fluorouracil treatment on SN-38 absorption from intestine in rats.

  Authors: Yoshihiko Shibayama, Yoshitaka Iwashita, Yoshimi Yoshikawa, Tomoko Kondo, Ryuji Ikeda, Yasuo Takeda, Takayuki Osada, Mitsuru Sugawara, Katsushi Yamada, Ken Iseki

  Biological & pharmaceutical bulletin. 01/2011; 34(9):1418-25.

  5-Fluorouracil (5-FU)-based chemotherapies with irinotecan have been applied for the treatment of cancers, and a common dose-limiting toxicity is neutropenia and diarrhea. In this study, we5-Fluorouracil (5-FU)-based chemotherapies with irinotecan have been applied for the treatment of cancers, and a common dose-limiting toxicity is neutropenia and diarrhea. In this study, we investigated the effect of 5-FU treatment on expression levels of drug transporters for SN-38 transportation and SN-38 absorption from the intestine following 5-FU treatment. Expression levels of several drug transporters and nuclear receptors in rats after 5-FU treatment were evaluated. SN-38 absorption from the intestine was evaluated by SN-38 concentration levels in serum following SN-38 injection into the intestine of 5-FU treated rats. The levels of renal multidrug resistance protein 2 (Mrp2) on day 4 after treatment (400 mg/kg) showed significant upregulation, 359.2 ± 33.2% (mean ± S.E.) of control. Mrp2 levels in the intestine were downregulated to 26.2 ± 8.4% of control. 5-FU treatment (400 mg/kg) also significantly downregurated expression levels of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) to 41.2 ± 14.7%, 15.7 ± 4.3% of control, respectively. To evaluate SN-38 absorption from the intestine, SN-38 was loaded in to the intestine on day 4 after 5-FU treatment. Pretreatment with 5-FU significantly increased SN-38 concentration in the blood 30, 60 and 90 min after SN-38 administration. The area under the curve for SN-38 in the 5-FU group was significantly higher than in vehicle groups. 5-FU treatment decreased expression levels of P-glycoprotein and Bcrp in intestine. The present study suggests that combination chemotherapy of 5-FU with irinotecan (CPT-11) may elevate SN-38 absorption from intestine.

• Using microarray analysis to evaluate genetic polymorphisms involved in the metabolism of environmental chemicals.

  Authors: Susumu Ban, Tomoko Kondo, Mayumi Ishizuka, Seiko Sasaki, Kanae Konishi, Noriaki Washino, Syoichi Fujita, Reiko Kishi

  Fukuoka igaku zasshi = Hukuoka acta medica. 06/2007; 98(5):208-14.

  The field of molecular biology currently faces the need for a comprehensive method of evaluating individual differences derived from genetic variation in the form of single nucleotide polymorphismsThe field of molecular biology currently faces the need for a comprehensive method of evaluating individual differences derived from genetic variation in the form of single nucleotide polymorphisms (SNPs). SNPs in human genes are generally considered to be very useful in determining inherited genetic disorders, susceptibility to certain diseases, and cancer predisposition. Quick and accurate discrimination of SNPs is the key characteristic of technology used in DNA diagnostics. For this study, we first developed a DNA microarray and then evaluated its efficacy by determining the detection ability and validity of this method. Using DNA obtained from 380 pregnant Japanese women, we examined 13 polymorphisms of 9 genes, which are associated with the metabolism of environmental chemical compounds found in high frequency among Japanese populations. The ability to detect CYP1A1 I462V, CYP1B1 L432V, GSTP1 I105V and AhR R554K gene polymorphisms was above 98%, and agreement rates when compared with real time PCR analysis methods (kappa values) showed high validity: 0.98 (0.96), 0.97 (0.93), 0.90 (0.81), 0.90 (0.91), respectively. While this DNA microarray analysis should prove important as a method for initial screening, it is still necessary that we find better methods for improving the detection of other gene polymorphisms not part of this study.

• Exposure of prepubertal female rats to inhaled di(2-ethylhexyl)phthalate affects the onset of puberty and postpubertal reproductive functions.

  Authors: Mingyue Ma, Tomoko Kondo, Susumu Ban, Tomohiro Umemura, Norie Kurahashi, Makoto Takeda, Reiko Kishi

  Toxicological sciences : an official journal of the Society of Toxicology. 10/2006; 93(1):164-71.

  We evaluated the effects of inhaled di(2-ethylhexyl)phthalate (DEHP) on the onset of puberty and on postpubertal reproductive functions in prepubertal female rats. DEHP was administered by inhalationWe evaluated the effects of inhaled di(2-ethylhexyl)phthalate (DEHP) on the onset of puberty and on postpubertal reproductive functions in prepubertal female rats. DEHP was administered by inhalation at doses of 0, 5, and 25 mg/m3 to groups of female rats for 6 h/day, 5 contiguous days/week from postnatal days (PNDs) 22 to 41 and to PND 84. The onset of puberty was determined by daily examination for vaginal opening (VO) and first estrous cycle. Reproductive function was evaluated by observing estrous cyclicity from PNDs 49 to 84. Upon completion of exposure, the rats were sacrificed at PND 42 and PNDs 85-88 during the diestrous stage. DEHP exposure advanced the age of VO and first estrous cycle, and serum cholesterol, luteinizing hormone, and estradiol levels were significantly elevated in the 25-mg/m3 DEHP group. Irregular estrous cycles were observed more frequently in DEHP-exposed rats, and serum cholesterol decreased in DEHP-exposed rats in adulthood; RT-PCR showed that the expression of aromatase mRNA, encoding a rate-limiting enzyme that catalyzes the conversion of testosterone to estradiol, was elevated in the 25-mg/m3 DEHP group. These data suggest that inhaled DEHP may advance the onset of puberty and alter postpubertal reproductive functions.

• Acute effects of styrene inhalation on the neuroendocrinological system of rats and the different effects in male and female rats.

  Authors: Tomohiro Umemura, Norie Kurahashi, Tomoko Kondo, Yoko Katakura, Fumihiro Sata, Toshio Kawai, Reiko Kishi

  Archives of toxicology. 12/2005; 79(11):653-9.

  There have been several epidemiological and experimental studies about styrene from the neuroendocrinological viewpoint. Some reported that styrene exposure affected the neuroendocrinological systemThere have been several epidemiological and experimental studies about styrene from the neuroendocrinological viewpoint. Some reported that styrene exposure affected the neuroendocrinological system and enhanced prolactin (PRL) secretion, but others have denied those effects. It was assumed that styrene exposure caused depletion of dopamine (DA), which is a PRL inhibitor, and that, in consequence, the PRL level increased. However, not only DA but also many other factors control PRL secretion. Therefore, the mechanism of hypersecretion of PRL has not yet been clearly elucidated. In addition, effects of styrene on the female reproductive system have been reported, but the susceptibility needs to be further studied. Therefore, to investigate what causes hypersecretion of PRL and how different the susceptibility is in males and females, we studied acute effects of styrene exposure on the neuroendocrinological system in male and female rats. Immediately after exposure to 150 ppm styrene vapor for 10 days (8 h/day), male and female rats were killed, and blood and brain samples were collected. The styrene concentration in blood, hormones such as PRL, growth hormone (GH) and thyroid-stimulating hormone (TSH) in plasma and neurotransmitters in various brain regions were measured. The styrene concentration in the blood of female rats was higher than that in male rats, and the PRL level was significantly increased in female exposed rats compared with controls. No significant change was observed in male rats. We did not observe any significant changes in DA, 5-hydroxytryptamine (5-HT) or their metabolites. Because neurotransmitters were not affected in either male or female rats, the mechanism enhancing PRL secretion remains unclear. These results suggest that styrene exposure may cause hypersecretion of PRL and that the sensitivity to styrene exposure of the female may be higher than that of the male.

• The effects of subacute inhalation of di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal Wistar rats.

  Authors: Norie Kurahashi, Tomoko Kondo, Minoru Omura, Tomohiro Umemura, Mingyue Ma, Reiko Kishi

  Journal of occupational health. 10/2005; 47(5):437-44.

  In animal studies using oral dosing for short periods, di (2-ethylhexyl) phthalate (DEHP) is well known for its reproductive toxicity, especially for its testicular toxicity. However, extending theIn animal studies using oral dosing for short periods, di (2-ethylhexyl) phthalate (DEHP) is well known for its reproductive toxicity, especially for its testicular toxicity. However, extending the period of DEHP exposure in prepubertal rats resulted in significant increases in testosterone. This suggests that the reproductive effect of DEHP might be associated with the timing and the term of exposure. Moreover, the route of exposure may induce differences in its effect because tissue levels of metabolites of DEHP after inhalation are thought to be different from those after oral administration. We researched the effects of inhalation of DEHP on testes of prepubertal rats. Our results showed that inhalation of DEHP by 4-wk-old male Wistar rats at doses of 5 or 25 mg/m(3), 6 h per day, for 4 and 8 wk significantly increased the concentration of plasma testosterone and weight of seminal vesicles. However, the concentration of luteinizing hormone (LH), follicular stimulating hormone (FSH) and the expression of mRNAs of androgen biosynthesis enzyme, cytochrome P450 cholesterol side-chain-cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450 17alpha-hydroxylase/17, 20 lyase (CYP17) and aromatase (CYP19) did not change. Rats with precocious testes did not increase in any of the DEHP groups. We also found that the estimated effective dose in this study was less than those reported in previous studies which used oral dosing. Our study showed that inhaled DEHP increased plasma testosterone concentrations in prepubertal rats and suggested that their effects were more sensitive to inhalation of DEHP than oral dosing.

• Single nucleotide polymorphisms in the promoter region of the interleukin-6 gene and the risk of recurrent pregnancy loss in Japanese women.

  Authors: Yasuaki Saijo, Fumihiro Sata, Hideto Yamada, Tomoko Kondo, Emi Hirayama Kato, Reiko Kishi

  Fertility and sterility. 03/2004; 81(2):374-8.

  OBJECTIVE: To investigate the relationships between recurrent pregnancy loss and single nucleotide polymorphisms (-634C-->G and -174G-->C genotypes) in the promoter region of the interleukin (IL)-6OBJECTIVE: To investigate the relationships between recurrent pregnancy loss and single nucleotide polymorphisms (-634C-->G and -174G-->C genotypes) in the promoter region of the interleukin (IL)-6 gene in the Japanese population. DESIGN: A case-control study. SETTING: Obstetrics and gynecology department of a university hospital. PATIENT(S): Cases were 76 women with recurrent pregnancy loss; controls were 93 fertile women. INTERVENTION(S): Determination of IL-6 promoter gene polymorphisms performed by polymerase chain reaction and gel electrophoresis. MAIN OUTCOME MEASURE(S): Frequency and distribution of the promoter region of the IL-6 gene allele. RESULTS: There was a significant difference in the -634C-->G genotype frequency (CC vs. CG/GG) between women with recurrent pregnancy loss and controls. The risk of recurrent pregnancy loss was lower in the carriers of the G allele than in women with the wild type (CC) (odds ratio = 0.46; 95% confidence interval = 0.24-0.91). On the other hand, we did not detect any carrier of -174C among the 169 subjects. CONCLUSION(S): The results suggest that, in the Japanese population, women carrying the -634G allele of the IL-6 gene might have a decreased risk of recurrent pregnancy loss.

• Visual dysfunction in workers exposed to a mixture of organic solvents.

  Authors: Yingyan Gong, Reiko Kishi, Setsuko Kasai, Yoko Katakura, Kyoko Fujiwara, Tomohiro Umemura, Tomoko Kondo, Tetsuro Sato, Fumihiro Sata, Eri Tsukishima, Shizuka Tozaki, Toshio Kawai, Yuriko Miyama

  Neurotoxicology. 09/2003; 24(4-5):703-10.

  The aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions includedThe aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions included color vision (CV), visual contrast sensitivity (CS) and visual evoked potentials (VEP). Test subjects were 182 workers at 53 furniture factories in the same industrial area of Japan. As control, a group consisted of 96 workers without exposure to any organic solvent was also tested. Exposure assessments were made both by the environmental concentration and biological monitoring. CV and CS tests were carried out for all the subjects. VEP was measured for 21 exposed subjects who were considered to have impaired CV and CS. In the results, the color confusion index (CCI) values of the exposed subjects were significantly higher than that of the age-matched controls (P<0.01). Their CS values were significantly lower than those in the controls at spatial frequencies of 6 and 12 cycles per degree (cpd) (P<0.01 and <0.05, respectively). A significant correlation between the concentration of urinary methylhippuric acid and contrast sensitivity was found by a multiple regression analysis (P<0.05). CCI showed a negative correlation at all spatial frequencies of CS in a simple regression analysis, no abnormal data were found by the VEP test in the exposed subjects who were found to have impaired CV and CS. The results suppose that a low concentration of the mixed organic solvents might affect the retina and optic nerve. However, it needs to be further researched if such an impact affects the Brodmann's areas of visual cortex in the brain.

• Visual Dysfunction in Workers Exposed to a Mixture of Organic Solvents

  Authors: Yingyan Gong, Reiko Kishi, Setsuko Kasai, Yoko Katakura, Kyoko Fujiwara, Tomohiro Umemura, Tomoko Kondo, Tetsuro Sato, Fumihiro Sata, Eri Tsukishima, Shizuka Tozaki, Toshio Kawai, Yuriko Miyama

  NeuroToxicology.

  The aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions includedThe aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions included color vision (CV), visual contrast sensitivity (CS) and visual evoked potentials (VEP). Test subjects were 182 workers at 53 furniture factories in the same industrial area of Japan. As control, a group consisted of 96 workers without exposure to any organic solvent was also tested. Exposure assessments were made both by the environmental concentration and biological monitoring. CV and CS tests were carried out for all the subjects. VEP was measured for 21 exposed subjects who were considered to have impaired CV and CS. In the results, the color confusion index (CCI) values of the exposed subjects were significantly higher than that of the age-matched controls (P<0.01). Their CS values were significantly lower than those in the controls at spatial frequencies of 6 and 12 cycles per degree (cpd) (P<0.01 and <0.05, respectively). A significant correlation between the concentration of urinary methylhippuric acid and contrast sensitivity was found by a multiple regression analysis (P<0.05). CCI showed a negative correlation at all spatial frequencies of CS in a simple regression analysis, no abnormal data were found by the VEP test in the exposed subjects who were found to have impaired CV and CS. The results suppose that a low concentration of the mixed organic solvents might affect the retina and optic nerve. However, it needs to be further researched if such an impact affects the Brodmann’s areas of visual cortex in the brain.

• Using Microarray Analysis to Evaluate Genetic Polymorphisms Involved in the Metabolism of Environmental Chemicals

  Authors: Susumu Ban, Tomoko Kondo, Mayumi Ishizuka, Seiko Sasaki, Kanae Konishi, Noriaki Washino, Syoichi Fujita, Reiko Kishi, 晋 坂, 朋子 近藤 [......] 正一 藤田, 玲子 岸, ススム バン, トモコ コンドウ, マユミ イシズカ, セイコ ササキ, カナエ コニシ, ノリアキ ワシノ, ショウイチ フジタ, レイコ キシ

  特集号　油症とPCB及びダイオキシン関連化合物　研究報告　第21集 The field of molecular biology currently faces the need for a comprehensive method of evaluating individual differences derived from genetic variation in the form of特集号　油症とPCB及びダイオキシン関連化合物　研究報告　第21集 The field of molecular biology currently faces the need for a comprehensive method of evaluating individual differences derived from genetic variation in the form of single nucleotide polymorphisms (SNPs). SNPs in human genes are generally considered to be very useful in determining inherited genetic disorders, susceptibility to certain diseases, and cancer predisposition. Quick and accurate discrimination of SNPs is the key characteristic of technology used in DNA diagnostics. For this study, we first developed a DNA microarray and then evaluated its efficacy by determining the detection ability and validity of this method. Using DNA obtained from 380 pregnant Japanese women, we examined 13 polymorphisms of 9 genes, which are associated with the metabolism of environmental chemical compounds found in high frequency among Japanese populations. The ability to detect CYP1A1 I462V, CYP1B1 L432V, GSTP1 I105V and AhR R554K gene polymorphisms was above 98%, and agreement rates when compared with real time PCR analysis methods (kappa values)showed high validity: 0. 98 (0.96), 0.97 (0.93), 0.90 (0.81), 0.90 (0.91), respectively. While this DNA microarray analysis should prove important as a method for initial screening,it is still necessary that we find better methods for improving the detection of other gene polymorphisms not part of this study. 近年，一遺伝子多型（SNPs）に由来する個々の感受性を包括的に評価する方法が必要とされている．ヒト遺伝子におけるSNP は，遺伝的な疾患，特定の疾病に対する感受性，癌などの素因のひとつとして考えられている．そのため，迅速で正確なSNPs判定法が求められている．本研究では，環境化学物質代謝に関与する遺伝子多型を判定するためのDNA マイクロアレイを開発し，その効力と信頼性を380人の日本人妊婦の血液を用いて，日本人で変異型.度の高い９遺伝子13多型について検討した．CYP1A1 I462V，CYP1B1 L432V，GSTP1 I105V，AhR R554K 遺伝子多型に対する検出力は98％以上の値を示すとともに，リアルタイムPCR 法による結果との比較による信頼度（κ係数）は，高い値を示した（それぞれ，0.98（0.96），0.97（0.93），0.90（0.81），0.90（0.91））．本研究のマイクロアレイ法は，検出できなかった遺伝子多型について改善する必要がある一方で，初期のスクリーニング方法として重要である．